煤矿工人轮班制与RAAS基因多态性交互作用对EH的影响
|
摘要
目的
原发性高血压（EH）是遗传因素和环境因素共同作用而引起的复杂性疾病，基因-基因、环境-环境以及基因-环境因素间交互作用在原发性高血压的发病中起重要的作用，因此应将遗传因素与环境因素结合起来探讨原发性高血压的病因。肾素-血管紧张素-醛固酮系统（RAAS）能够调节血容量和血压水平，在原发性高血压的发病及心血管病理发生发展中起重要作用，编码该系统的基因就成为原发性高血压重要的侯选基因。轮换班制度作为一种职业性社会心理因素，干扰生物节律，直接或间接引起一系列生理、心理等方面的应激反应。轮换班制度作为一种潜在的危险因素容易诱发心血管疾病等慢性疾病。本研究是以煤矿井下作业工人为研究对象的病例-对照研究，从环境因素和遗传因素两方面分析轮换班和基因多态性与原发性高血压的关系，探讨轮换班制度与基因多态性交互作用对原发性高血压的影响，从而为煤矿工人原发性高血压的防治提供理论依据。
内容与方法
1研究对象的选择
随机选择参加2010年职业健康检查的某地区汉族男性煤矿井下作业工人1048例为研究对象。严格按照纳入排除标准选择病例和对照。研究对象经知情同意后入选。
2现场流行病学调查
自行设计职业流行病学调查表，经预调查反复修改后使用；统一培训调查员，采用面对面访谈式问卷调查；调查内容包括人口学资料、职业史、家族史、个人史（吸烟、饮酒等）、以及饮食习惯等；对被调查对象进行测量身高、体重、血压等体格检查。
3实验室检测
抽取清晨空腹静脉血5ml，用于生化指标检测及基因组DNA提取。全自动生化分析仪检测血糖（GLU）、尿酸（UA）、甘油三酯（TG）、总胆固醇（TC）、高密度脂蛋白（HDLC）、低密度脂蛋白（LDLC）、高敏C反应蛋白（hs-CRP）等生化指标。低渗法分离白细胞，酚氯仿法提取基因组DNA；聚合酶链反应（PCR）检测血管紧张素转换酶（ACE）插入/缺失（I/D）序列多态性；限制性片段长度多态性（PCR-RFLP）检测血管紧张素原（AGT）基因M235T位点、血管紧张素II1型受体（AT1R）基因A1166C位点和醛固酮合成酶（CYP11B2）基因-344T/C位点的多态性。
4统计分析
Epidata3.0数据库管理软件建立数据库，SPSS16.0、SAS8.0、MDR2.0统计分析软件进行数据分析。计量资料以均数±标准差（x|-±s）表示，组间比较采用t检验或方差分析；计数资料组间比较采用χ~2检验或确切概率法（fisher’s test）。
采用χ~2检验分析基因型分布是否符合Hardy-Weinberg遗传平衡定律，比较病例组和对照组之间基因型和等位基因的分布；单因素条件logistic回归分析轮换班、基因多态性与原发性高血压的关系；采用叉生分析、多因素logistic回归、多因子降维法分析基因-基因和环境-基因交互作用对原发性高血压的影响。
检验水准α=0.05，P<0.05，差异有统计学意义。
结果
1环境因素与原发性高血压的关系
单因素分析表明，超重或肥胖者发生原发性高血压的危险是正常体重者的2.14（95%CI:1.67～2.74）倍，有高血压家族史者发生原发性高血压的危险增高1.49（95%CI:1.14～1.94）倍，从事轮换工作发生原发性高血压的危险是正常固定班的1.45（95%CI:1.12～1.86）倍，经常参加体育锻炼者发生原发性高血压的危险是不经常参加体育锻炼的0.64（95%CI:0.49～0.84）倍，打鼾者发生原发性高血压的危险是不打鼾者的1.28（95%CI:1.09～1.51）倍，差异有统计学意义（P<0.05）；饮食方面食盐摄入量较多可使原发性高血压的发病风险增加1.20（95%CI:1.04～1.39）倍，较多食用粗粮、蔬菜、水果则可降低原发性高血压的发病风险。病例组和对照组血液生化指标GLU、UA、TG、TC、HDLC、LDLC水平比较，差异有统计学意义（P<0.05），其水平异常增高可不同程度地增加或降低原发性高血压的发病危险。
多因素logistic回归分析在排除研究因素间的干扰、控制混杂因素的影响后，表明BMI≥24kg/m2、高血压家族史、轮换班、血糖、TC/HDLC≥4.5、LDLC≥2.7mmol可分别使原发性高血压的发病危险增加2.09（95%CI:1.59～2.74）、1.47（95%CI:1.09～1.97）、1.44（95%CI:1.09～1.90）、1.45（95%CI:1.04～2.01）、2.39（95%CI:1.69～3.38）和2.18（95%CI:1.62～2.95）倍，差异有统计学意义（P<0.05），是原发性高血压的危险因素；增加水果摄入量、体育锻炼使原发性高血压的发病危险降低，其OR（95%CI）分别为0.65（0.49～0.88）和0.74（0.61～0.91），差异有显著性意义（P<0.05），是原发性高血压的保护性因素。
2基因多态性与原发性高血压的关系
AGT基因M235T位点MM、MT、TT基因型频率在病例组和对照组分别为13.93%、46.37%、39.70%和16.60%、52.48%、30.92%，基因型在两组中的分布有显著性差异（χ~2=8.92，P=0.01）；病例组携带T等位基因的频率（62.88%）高于对照组（57.16%），差异有统计学意义（χ~2=7.16，P=0.01），但多因素分析尚不能认为AGT基因M235T多态性与原发性高血压发病风险有关（P>0.05）。
ACE基因插入/缺失序列II、ID、DD基因型在病例组和对照组中频率分别为45.99%、39.31%、14.70%和49.81%、40.46%、9.73%，基因型在两组中的分布比较，差异无统计学意义（χ~2=6.16，P=0.05）；病例组携带D等位基因的频率（34.35%）高于对照组（29.96%），差异有统计学意义（χ~2=4.63，P=0.03）。多因素分析表明携带DD基因型者发生原发性高血压的风险增加1.73（95%CI:1.12～2.68）倍，差异有统计学意义（P<0.05），ACE基因DD基因型可能是原发性高血压的易感基因型。
AT1R基因A1166C位点AA基因型频率病例组（91.79%）高于对照组（87.60%），组间分布有显著性差异（χ~2=5.00，P=0.03）；等位基因A和C的分布在两组间无显著性差异（P>0.05）。多因素分析表明携带C等位基因的基因型发生原发性高血压的风险是AA基因型的0.55（95%CI:0.35～0.87）倍，差异有统计学意义（P<0.05），提示A等位基因可能是原发性高血压的易感基因。
CYP11B2基因-334T/C位点TT、TC、CC基因型频率在病例组和对照组分别为50.76%、41.22%、8.02%和49.24%、42.56%、8.20%；病例组携带T等位基因和C等位基因的频率分别是71.37%、28.63%，对照组分别为70.52%、29.48%，两组中基因型及等位基因分布均无显著性差异（P>0.05），且多因素分析表明不能认为CYP11B2基因与原发性高血压的发病有关。
3基因-基因交互作用分析
叉生分析方法分析基因间相加模型的交互作用，结果显示AGT基因与ACE基因间交互项OR_(int)=0.10<1，对交互作用进行显著性检验，差异有统计学意义（χ~2=19.26, P=0.01）；AGT基因与CYP11B2基因交互项OR_(int)=8.54，对交互作用进行显著性检验，差异有显著性（χ~2=16.47, P=0.04）；AGT基因与AT1R基因间、ACE基因与AT1R基因间交互项OR_(int)值分别为1.10和1.10，对交互作用进行显著性检验，差异均有统计学意义（P<0.05）；未发现ACE基因与CYP11B2基因间和AT1R基因与CYP11B2基因间存在基于相加模型的交互作用（P>0.05）。
将各基因变量及其交互项共同引入Logistic回归模型，同时控制轮换班、体重指数、高血压家族史等因素的影响，分析基因间交互作用，尚不能认为各基因在原发性高血压的发生发展过程中存在基于相乘模型的交互作用（P>0.05）。应用MDR方法分析基因间交互作用时所有模型的显著性检验均无统计学意义（P>0.05），不能认为基因间存在交互作用。
4基因-轮换班交互作用分析
利用叉生分析轮换班与基因间基于相加模型的交互作用，结果表明轮换班与AGT、ACE、AT1R基因交互项OR_(int)<1，且差异均有显著性（P<0.05），提示存在负交互作用；未发现轮换班与CYP11B2基因存在基于相加模型的交互作用（P>0.05）。将轮换班、基因变量以及两者的交互项共同引入logistic回归模型，分析轮换班与基因基于相乘模型的交互作用与原发性高血压的关系，轮换班与AGT、ACE、AT1R、CYP11B2基因交互项ORnt值分别为1.05(95%CI:0.70～1.56)、0.84(95%CI:0.56～1.25)、0.58(95%CI:0.23～1.47)、0.81(95%CI:0.52～1.27)，交互作用显著性检验均无统计学意义（P>0.05），尚不能认为轮换班与各基因间存在相乘模型的交互作用。
5基因-高血压家族史交互作用分析
利用叉生分析高血压家族史与基因间基于相加模型的交互作用，高血压家族史与AGT、AT1R基因交互项ORnt值分别为1.40和1.12，差异有显著性（P<0.05）；高血压家族史与ACE基因交互项ORnt值=0.71，差异有统计学意义（P<0.05）；高血压家族史与CYP11B2基因间交互作用显著性检验，差异无统计学意义（P>0.05）。Logistic回归分析高血压家族史与基因间基于相乘模型的交互作用与原发性高血压的关系，高血压家族史与AGT、ACE、AT1R、CYP11B2基因交互项ORnt值分别为1.12(95%CI:0.73～1.72)、1.49(95%CI:0.96～2.30)、1.35(95%CI:0.50～3.66)、1.03(95%CI:0.64～1.64)，交互作用显著性检验均无统计学意义（P>0.05），尚不能认为高血压家族史与各基因交互作用与原发性高血压有关。
6基因-体重指数交互作用分析
叉生分析体重指数与基因间基于相加模型的交互作用，体重指数与AGT、ACE、AT1R基因交互项ORnt值分别为0.61、0.14、0.58，差异有显著性（P<0.05）；体重指数与CYP11B2基因间交互作用显著性检验，差异有统计学意义（P<0.05）。logistic回归分析体重指数与基因间基于相乘模型的交互作用与原发性高血压的关系，体重指数与AGT、AT1R、CYP11B2基因交互项ORnt值分别为1.11(95%CI:0.75～1.64)、0.66(95%CI:0.27～1.62)、1.29(95%CI:0.84～1.99)，交互作用显著性检验均无统计学意义（P>0.05）；体重指数与ACE基因间交互项OR_(int)=0.61(95%CI:0.41～0.90)，交互作用显著性检验有统计学意义。
7MDR法分析基因-环境交互作用
MDR方法对基因-环境交互作用分析结果表明，4因子和7因子模型为基因-环境因素MDR交互作用模型，轮换班与体重指数、水果摄入量、TC/HDLC、AGT、ACE、CYP11B2存在交互作用，并能增加原发性高血压的发病危险。
结论
1轮换班可能是原发性高血压的危险因素。
2ACE基因I/D序列多态性和AT1R基因A1166C基因多态性与原发性高血压有关，ACE基因DD基因型和AT1R基因A1166C基因多态性AA基因型可能是原发性高血压的易感基因型。
3轮换班与ACE基因I/D多态性、AT1R基因A1166C位点多态性间存在基于相加模型的交互作用；轮换班与体重指数、水果摄入量、TC/HDLC、AGT、ACE、CYP11B2存在交互作用，并能增加原发性高血压的发病危险；未发现基因间存在交互作用。
Objectives
Essential hypertension (EH) is a complex disease caused by genetic andenvironmental factors. We should explore mechanism of EH combined genetic factorswith environmental factors, for which the interaction between genetic factors andenvironmental factors plays an important role in the pathogenesis of EH. Therenin-angiotensin-aldosterone system (RAAS), which can regulate blood volume andblood pressure levels, is important for the pathogenesis and pathology ofcardiovascular disease, therefore the gene from RAAS maybe important candidategenes of hypertension. Shift work as a potential risk factor is likely to causecardiovascular disease and other chronic diseases. A case-control study based on coalworkers was designed to analyze the relationship among gene polymorphisms, shiftwork and EH, the interaction of gene-environmental was analyzed too.
Methods
1Choice of object
A case-control study was adopted.1048coal workers, who acceptedoccupational health examination were chosen to participate in this study.
2Field epidemiological investigation
Design occupational epidemiology questionnaire, face-to-face interview wasconducted. The survey contents including demographic data, occupational history,family history, personal history (smoking, drinking, etc), as well as eating habits, etc.;measuring height, weight, blood pressure and other physical examination.
3Laboratory test
5ml venous blood were extracted in early morning, some used for the detectionof biochemical indicators including blood glucose (GLU), uric acid (UA),triglycerides (TG), total cholesterol (TC), high-density lipoprotein (HDLC), lowdensity lipoprotein (LDLC), C-reactive protein (CRP) and so on. Separate whiteblood cells with hyptonic method, and genomic DNA were extracted with phenol-chloroform methods. Polymerase chain reaction (PCR) was used to detectpolymorphism of insertion/deletion (I/D) polymorphism of angiotensin-convertingenzyme (ACE). The polymorphisms of AGT-M235T, AT1R-A1166C andCYP11B2-344T/C gene were detected by polymerase chain reaction-restrictionfragment length polymorphism (PCR-RFLP).
4Statistical Analysis
Database was established with Epi-data3.0, SPSS16.0, SAS8.0and MDR2.0statistical analysis software were used for data analysis. The measurement data wereexpressed as x±s, t test or ANOVAS were used to compare the difference betweengroups.
The χ~2test were used to analyze whether distribution of genotype in accordancewith Hardy-Weinberg genetic equilibrium or not; and compared the distribution ofgenotype and allele between case and control groups; Univariate analysis analyzed therelationship of environmental factors and gene polymorphism with essentialhypertension risk. Using stratifies analysis and multivariate analysis methodsanalyzed the relationship between interaction of genes-genes, environment-genewith EH.
Test level of α=0.05, P <0.05expressed the difference was statisticallysignificant.
Results
1Environmental factors with EH
Univariate analysis demonstrated that overweight or obese increased the risk ofEH2.14(95%CI:1.67~2.74) times; family history of hypertension increased therisk of EH1.49(95%CI:1.14~1.94) times; shift work increase the risk of EH1.45(95%CI:1.12~1.86) times; participate in regular physical exercise increased the riskof suffering from EH0.64(95%CI:0.49~0.84) times compared with not participatein physical exercise; snorers with the risk of EH was1.28(95%CI:1.09~1.51) timescompared with not snorers, and the difference was statistically significant (P <0.05).Much more salt intake is likely to increase the risk of EH of1.20(95%CI:1.04~1.39) times, but eat more coarse grains, vegetables, fruits may reduce the risk of EH.There was significant difference of GLU, UA, TG, TC, HDLC and LDLC levelbetween case group and control group.
With multivariate analysis, BMI≥24kg/m~2, family history of hypertension, shift work, blood glucose, TC/HDLC≥4.5, LDLC≥2.7mmol may increase the risk ofEH of2.09(95%CI:1.59~2.74).1.47(95%CI:1.09~1.966),1.44(95%CI:1.09~1.90),1.45(95%CI:1.04~2.01),2.39(95%CI:1.69~3.38) and2.18(95%CI:1.62~2.95) times separately, and the difference was statistically significant (P <0.05),they were risk factors of EH. Increase intake of fruit, more physical exercise mayreduced the risk of EH, and the OR (95%CI) were0.65(0.49~0.88) and0.74(0.61~0.91), the difference was significant (P <0.05), they were protective factors of EH.
2The relationship between gene polymorphism and essential hypertension
There were significant differences in M235T genotypes and allele frequencies ofAGT gene between cases and control group (χ~2=8.92, P=0.01); the T allele frequencyin case group (62.88%) was higher than control group (57.16%), the difference wassignificant (χ~2=7.16, P=0.01). However, there is not yet that M235T polymorphism ofAGT gene is related with EH (P>0.05) in multivariate analysis.
The II, ID and DD genotype frequency of ACE gene in cases and control groupswere45.99%,39.31%,14.70%and49.81%,40.46%,9.73%separately, and there wasno significant difference of distribution of genotype between case and control groups(χ~2=6.16, P=0.05). The allele frequency of D in case group (34.35%)was higher thancontrol group (29.96%), the difference was significant (χ~2=4.63, P=0.03). Multivariateanalysis revealed that carrying DD genotype increased the risk of EH of1.73(95%CI:1.12~2.68) times, the difference was statistically significant (P <0.05), DD genotypeof ACE gene might be the susceptible genotypes for EH.
There was significant difference in distribution of AA genotype of AT1R genebetween case and control groups(χ~2=5.00, P=0.03). The distribution of alleles A andC was no significant difference between the two groups (P>0.05). Multivariateanalysis showed that the genotype that carrying C allele increase the risk of EH0.55(95%CI:0.35~0.87) times than AA genotype, the difference was statisticallysignificant (P <0.05), which suggesting that A allele may be susceptible gene for EH.
TT, TC and CC genotype frequencies of CYP11B2gene-334T/C loci in case andcontrol groups were50.76%,41.22%,8.02%and49.24%,42.56%,8.20%respectively; carrying T allele and C allele frequencies in case group were71.37%,28.63%, in control group were70.52%,29.48%, there was no significant difference ofgenotype and allele distribution in the two groups (P>0.05), and multivariate analysisconcluded that it can not be considered CYP11B2gene was related with thepathogenesis of EH.
3Analysis of interaction among genes
Stratify analysis method was used to analyze interaction based on the additivemodel among the genes, the results showed that there were negative interactionbetween the AGT gene and ACE gene (χ~2=19.26, P=0.01); There was significantdifference of interactions between AGT gene and CYP11B2gene (χ~2=16.47, P=0.04),between AGT gene and AT1R gene, between ACE gene and AT1R gene. Still, nosignificant interactions based on the additive model between ACE gene and CYP11B2gene, AT1R gene and CYP11B2gene were founded.
After adjusted shift work, BMI, family history of hypertension and other factors,gene variables and their interaction terms were introduced to logistic regression modelfor the multiplicative model of interaction analysis, the results show that there was notinteraction among genes during the development of EH(P>0.05).
4Interaction analysis between gene and shift work
Stratify analysis method was used to analyze interaction based on the additivemodel between shift work and gene, the results showed that there was negativeinteraction between shift work and AGT、ACE、AT1R genes, and the differences weresignificant (P<0.05). Shift work, genetic variables, and the interaction term wereintroduced to logistic regression model, to analyze the relationship of shift work andgene interaction based on the multiplicative model with EH, the interaction OR_(int)values of shift work and AGT、ACE、AT1R、CYP11B2genes were1.05(95%CI:0.70~1.56),0.84(95%CI:0.56~1.25),0.58(95%CI:0.23~1.47),0.81(95%CI:0.52~1.27) separately, there were not statistically significant (P>0.05), still it can notbelieve that there were interactions based on multiplicative model between shift workand each gene.
5Interaction analysis between gene and family history of hypertension
Stratify analysis method was used to analyze interaction based on the additivemodel between family history of hypertension and genes, it found that OR_(int) values ofinteraction terms between family history of hypertension and AGT, AT1R, ACE genewas1.40,1.12,0.71respectively, the difference were significantly (P<0.05); therewas no interactions between family history of hypertension and CYP11B2gene.Logistic regression analysis was used to analyze the interaction between familyhistory and gene based on multiplicative model, it can not believe that there weresignificant difference between family history of hypertension and AGT、ACE、AT1R、 CYP11B2genes.
6Interaction analysis between gene and BMI
Stratify analysis method was used to analyze interaction based on the additivemodel between BMI and genes, it concluded that there were significant difference ininteractions between BMI and AGT, ACE, AT1R, CYP11B2genes(P<0.05). Logisticregression analysis was used to analyze the relationship of interaction between BMIand genes based on multiplicative model, OR_(int)values of interaction terms betweenBMI and AGT、AT1R、CYP11B2were1.11(95%CI:0.75～1.64)、0.66(95%CI:0.27～1.62)、1.29(95%CI:0.84～1.99) respectively, there were no significantdifference in interactions(P>0.05). However, there was interactions between BMIand ACE gene.
7Gene-environment interaction analysis with MDR method
MDR method was used to analyze gene-environment interaction, the resultsshowed that the4-factor and7-factor model were MDR interaction models of gene-environmental factors. There were interactions between shift work and BMI, fruitintake, TC/HDLC, AGT, ACE, CYP11B2gene, which can increase the risk of theincidence of EH.
Conlusions
1Shift work may be risk factor of EH.
2The polymorphism of sequence I/D of ACE gene and A1166C of AT1R gene mightrelated with EH. DD genotype of ACE gene and AA genotype of AT1R gene may besusceptible genotype of EH.
3There were interactions based on additive model between shift work and ACE geneI/D polymorphism, AT1R gene A1166C polymorphism. Still there were interactionsbetween shift work and BMI, fruit intake, TC/HDLC AGT, ACE, of CYP11B2, andwhich could increase the risk of the incidence of EH.
原发性高血压（EH）是遗传因素和环境因素共同作用而引起的复杂性疾病，基因-基因、环境-环境以及基因-环境因素间交互作用在原发性高血压的发病中起重要的作用，因此应将遗传因素与环境因素结合起来探讨原发性高血压的病因。肾素-血管紧张素-醛固酮系统（RAAS）能够调节血容量和血压水平，在原发性高血压的发病及心血管病理发生发展中起重要作用，编码该系统的基因就成为原发性高血压重要的侯选基因。轮换班制度作为一种职业性社会心理因素，干扰生物节律，直接或间接引起一系列生理、心理等方面的应激反应。轮换班制度作为一种潜在的危险因素容易诱发心血管疾病等慢性疾病。本研究是以煤矿井下作业工人为研究对象的病例-对照研究，从环境因素和遗传因素两方面分析轮换班和基因多态性与原发性高血压的关系，探讨轮换班制度与基因多态性交互作用对原发性高血压的影响，从而为煤矿工人原发性高血压的防治提供理论依据。
内容与方法
1研究对象的选择
随机选择参加2010年职业健康检查的某地区汉族男性煤矿井下作业工人1048例为研究对象。严格按照纳入排除标准选择病例和对照。研究对象经知情同意后入选。
2现场流行病学调查
自行设计职业流行病学调查表，经预调查反复修改后使用；统一培训调查员，采用面对面访谈式问卷调查；调查内容包括人口学资料、职业史、家族史、个人史（吸烟、饮酒等）、以及饮食习惯等；对被调查对象进行测量身高、体重、血压等体格检查。
3实验室检测
抽取清晨空腹静脉血5ml，用于生化指标检测及基因组DNA提取。全自动生化分析仪检测血糖（GLU）、尿酸（UA）、甘油三酯（TG）、总胆固醇（TC）、高密度脂蛋白（HDLC）、低密度脂蛋白（LDLC）、高敏C反应蛋白（hs-CRP）等生化指标。低渗法分离白细胞，酚氯仿法提取基因组DNA；聚合酶链反应（PCR）检测血管紧张素转换酶（ACE）插入/缺失（I/D）序列多态性；限制性片段长度多态性（PCR-RFLP）检测血管紧张素原（AGT）基因M235T位点、血管紧张素II1型受体（AT1R）基因A1166C位点和醛固酮合成酶（CYP11B2）基因-344T/C位点的多态性。
4统计分析
Epidata3.0数据库管理软件建立数据库，SPSS16.0、SAS8.0、MDR2.0统计分析软件进行数据分析。计量资料以均数±标准差（x|-±s）表示，组间比较采用t检验或方差分析；计数资料组间比较采用χ~2检验或确切概率法（fisher’s test）。
采用χ~2检验分析基因型分布是否符合Hardy-Weinberg遗传平衡定律，比较病例组和对照组之间基因型和等位基因的分布；单因素条件logistic回归分析轮换班、基因多态性与原发性高血压的关系；采用叉生分析、多因素logistic回归、多因子降维法分析基因-基因和环境-基因交互作用对原发性高血压的影响。
检验水准α=0.05，P<0.05，差异有统计学意义。
结果
1环境因素与原发性高血压的关系
单因素分析表明，超重或肥胖者发生原发性高血压的危险是正常体重者的2.14（95%CI:1.67～2.74）倍，有高血压家族史者发生原发性高血压的危险增高1.49（95%CI:1.14～1.94）倍，从事轮换工作发生原发性高血压的危险是正常固定班的1.45（95%CI:1.12～1.86）倍，经常参加体育锻炼者发生原发性高血压的危险是不经常参加体育锻炼的0.64（95%CI:0.49～0.84）倍，打鼾者发生原发性高血压的危险是不打鼾者的1.28（95%CI:1.09～1.51）倍，差异有统计学意义（P<0.05）；饮食方面食盐摄入量较多可使原发性高血压的发病风险增加1.20（95%CI:1.04～1.39）倍，较多食用粗粮、蔬菜、水果则可降低原发性高血压的发病风险。病例组和对照组血液生化指标GLU、UA、TG、TC、HDLC、LDLC水平比较，差异有统计学意义（P<0.05），其水平异常增高可不同程度地增加或降低原发性高血压的发病危险。
多因素logistic回归分析在排除研究因素间的干扰、控制混杂因素的影响后，表明BMI≥24kg/m2、高血压家族史、轮换班、血糖、TC/HDLC≥4.5、LDLC≥2.7mmol可分别使原发性高血压的发病危险增加2.09（95%CI:1.59～2.74）、1.47（95%CI:1.09～1.97）、1.44（95%CI:1.09～1.90）、1.45（95%CI:1.04～2.01）、2.39（95%CI:1.69～3.38）和2.18（95%CI:1.62～2.95）倍，差异有统计学意义（P<0.05），是原发性高血压的危险因素；增加水果摄入量、体育锻炼使原发性高血压的发病危险降低，其OR（95%CI）分别为0.65（0.49～0.88）和0.74（0.61～0.91），差异有显著性意义（P<0.05），是原发性高血压的保护性因素。
2基因多态性与原发性高血压的关系
AGT基因M235T位点MM、MT、TT基因型频率在病例组和对照组分别为13.93%、46.37%、39.70%和16.60%、52.48%、30.92%，基因型在两组中的分布有显著性差异（χ~2=8.92，P=0.01）；病例组携带T等位基因的频率（62.88%）高于对照组（57.16%），差异有统计学意义（χ~2=7.16，P=0.01），但多因素分析尚不能认为AGT基因M235T多态性与原发性高血压发病风险有关（P>0.05）。
ACE基因插入/缺失序列II、ID、DD基因型在病例组和对照组中频率分别为45.99%、39.31%、14.70%和49.81%、40.46%、9.73%，基因型在两组中的分布比较，差异无统计学意义（χ~2=6.16，P=0.05）；病例组携带D等位基因的频率（34.35%）高于对照组（29.96%），差异有统计学意义（χ~2=4.63，P=0.03）。多因素分析表明携带DD基因型者发生原发性高血压的风险增加1.73（95%CI:1.12～2.68）倍，差异有统计学意义（P<0.05），ACE基因DD基因型可能是原发性高血压的易感基因型。
AT1R基因A1166C位点AA基因型频率病例组（91.79%）高于对照组（87.60%），组间分布有显著性差异（χ~2=5.00，P=0.03）；等位基因A和C的分布在两组间无显著性差异（P>0.05）。多因素分析表明携带C等位基因的基因型发生原发性高血压的风险是AA基因型的0.55（95%CI:0.35～0.87）倍，差异有统计学意义（P<0.05），提示A等位基因可能是原发性高血压的易感基因。
CYP11B2基因-334T/C位点TT、TC、CC基因型频率在病例组和对照组分别为50.76%、41.22%、8.02%和49.24%、42.56%、8.20%；病例组携带T等位基因和C等位基因的频率分别是71.37%、28.63%，对照组分别为70.52%、29.48%，两组中基因型及等位基因分布均无显著性差异（P>0.05），且多因素分析表明不能认为CYP11B2基因与原发性高血压的发病有关。
3基因-基因交互作用分析
叉生分析方法分析基因间相加模型的交互作用，结果显示AGT基因与ACE基因间交互项OR_(int)=0.10<1，对交互作用进行显著性检验，差异有统计学意义（χ~2=19.26, P=0.01）；AGT基因与CYP11B2基因交互项OR_(int)=8.54，对交互作用进行显著性检验，差异有显著性（χ~2=16.47, P=0.04）；AGT基因与AT1R基因间、ACE基因与AT1R基因间交互项OR_(int)值分别为1.10和1.10，对交互作用进行显著性检验，差异均有统计学意义（P<0.05）；未发现ACE基因与CYP11B2基因间和AT1R基因与CYP11B2基因间存在基于相加模型的交互作用（P>0.05）。
将各基因变量及其交互项共同引入Logistic回归模型，同时控制轮换班、体重指数、高血压家族史等因素的影响，分析基因间交互作用，尚不能认为各基因在原发性高血压的发生发展过程中存在基于相乘模型的交互作用（P>0.05）。应用MDR方法分析基因间交互作用时所有模型的显著性检验均无统计学意义（P>0.05），不能认为基因间存在交互作用。
4基因-轮换班交互作用分析
利用叉生分析轮换班与基因间基于相加模型的交互作用，结果表明轮换班与AGT、ACE、AT1R基因交互项OR_(int)<1，且差异均有显著性（P<0.05），提示存在负交互作用；未发现轮换班与CYP11B2基因存在基于相加模型的交互作用（P>0.05）。将轮换班、基因变量以及两者的交互项共同引入logistic回归模型，分析轮换班与基因基于相乘模型的交互作用与原发性高血压的关系，轮换班与AGT、ACE、AT1R、CYP11B2基因交互项ORnt值分别为1.05(95%CI:0.70～1.56)、0.84(95%CI:0.56～1.25)、0.58(95%CI:0.23～1.47)、0.81(95%CI:0.52～1.27)，交互作用显著性检验均无统计学意义（P>0.05），尚不能认为轮换班与各基因间存在相乘模型的交互作用。
5基因-高血压家族史交互作用分析
利用叉生分析高血压家族史与基因间基于相加模型的交互作用，高血压家族史与AGT、AT1R基因交互项ORnt值分别为1.40和1.12，差异有显著性（P<0.05）；高血压家族史与ACE基因交互项ORnt值=0.71，差异有统计学意义（P<0.05）；高血压家族史与CYP11B2基因间交互作用显著性检验，差异无统计学意义（P>0.05）。Logistic回归分析高血压家族史与基因间基于相乘模型的交互作用与原发性高血压的关系，高血压家族史与AGT、ACE、AT1R、CYP11B2基因交互项ORnt值分别为1.12(95%CI:0.73～1.72)、1.49(95%CI:0.96～2.30)、1.35(95%CI:0.50～3.66)、1.03(95%CI:0.64～1.64)，交互作用显著性检验均无统计学意义（P>0.05），尚不能认为高血压家族史与各基因交互作用与原发性高血压有关。
6基因-体重指数交互作用分析
叉生分析体重指数与基因间基于相加模型的交互作用，体重指数与AGT、ACE、AT1R基因交互项ORnt值分别为0.61、0.14、0.58，差异有显著性（P<0.05）；体重指数与CYP11B2基因间交互作用显著性检验，差异有统计学意义（P<0.05）。logistic回归分析体重指数与基因间基于相乘模型的交互作用与原发性高血压的关系，体重指数与AGT、AT1R、CYP11B2基因交互项ORnt值分别为1.11(95%CI:0.75～1.64)、0.66(95%CI:0.27～1.62)、1.29(95%CI:0.84～1.99)，交互作用显著性检验均无统计学意义（P>0.05）；体重指数与ACE基因间交互项OR_(int)=0.61(95%CI:0.41～0.90)，交互作用显著性检验有统计学意义。
7MDR法分析基因-环境交互作用
MDR方法对基因-环境交互作用分析结果表明，4因子和7因子模型为基因-环境因素MDR交互作用模型，轮换班与体重指数、水果摄入量、TC/HDLC、AGT、ACE、CYP11B2存在交互作用，并能增加原发性高血压的发病危险。
结论
1轮换班可能是原发性高血压的危险因素。
2ACE基因I/D序列多态性和AT1R基因A1166C基因多态性与原发性高血压有关，ACE基因DD基因型和AT1R基因A1166C基因多态性AA基因型可能是原发性高血压的易感基因型。
3轮换班与ACE基因I/D多态性、AT1R基因A1166C位点多态性间存在基于相加模型的交互作用；轮换班与体重指数、水果摄入量、TC/HDLC、AGT、ACE、CYP11B2存在交互作用，并能增加原发性高血压的发病危险；未发现基因间存在交互作用。
Objectives
Essential hypertension (EH) is a complex disease caused by genetic andenvironmental factors. We should explore mechanism of EH combined genetic factorswith environmental factors, for which the interaction between genetic factors andenvironmental factors plays an important role in the pathogenesis of EH. Therenin-angiotensin-aldosterone system (RAAS), which can regulate blood volume andblood pressure levels, is important for the pathogenesis and pathology ofcardiovascular disease, therefore the gene from RAAS maybe important candidategenes of hypertension. Shift work as a potential risk factor is likely to causecardiovascular disease and other chronic diseases. A case-control study based on coalworkers was designed to analyze the relationship among gene polymorphisms, shiftwork and EH, the interaction of gene-environmental was analyzed too.
Methods
1Choice of object
A case-control study was adopted.1048coal workers, who acceptedoccupational health examination were chosen to participate in this study.
2Field epidemiological investigation
Design occupational epidemiology questionnaire, face-to-face interview wasconducted. The survey contents including demographic data, occupational history,family history, personal history (smoking, drinking, etc), as well as eating habits, etc.;measuring height, weight, blood pressure and other physical examination.
3Laboratory test
5ml venous blood were extracted in early morning, some used for the detectionof biochemical indicators including blood glucose (GLU), uric acid (UA),triglycerides (TG), total cholesterol (TC), high-density lipoprotein (HDLC), lowdensity lipoprotein (LDLC), C-reactive protein (CRP) and so on. Separate whiteblood cells with hyptonic method, and genomic DNA were extracted with phenol-chloroform methods. Polymerase chain reaction (PCR) was used to detectpolymorphism of insertion/deletion (I/D) polymorphism of angiotensin-convertingenzyme (ACE). The polymorphisms of AGT-M235T, AT1R-A1166C andCYP11B2-344T/C gene were detected by polymerase chain reaction-restrictionfragment length polymorphism (PCR-RFLP).
4Statistical Analysis
Database was established with Epi-data3.0, SPSS16.0, SAS8.0and MDR2.0statistical analysis software were used for data analysis. The measurement data wereexpressed as x±s, t test or ANOVAS were used to compare the difference betweengroups.
The χ~2test were used to analyze whether distribution of genotype in accordancewith Hardy-Weinberg genetic equilibrium or not; and compared the distribution ofgenotype and allele between case and control groups; Univariate analysis analyzed therelationship of environmental factors and gene polymorphism with essentialhypertension risk. Using stratifies analysis and multivariate analysis methodsanalyzed the relationship between interaction of genes-genes, environment-genewith EH.
Test level of α=0.05, P <0.05expressed the difference was statisticallysignificant.
Results
1Environmental factors with EH
Univariate analysis demonstrated that overweight or obese increased the risk ofEH2.14(95%CI:1.67~2.74) times; family history of hypertension increased therisk of EH1.49(95%CI:1.14~1.94) times; shift work increase the risk of EH1.45(95%CI:1.12~1.86) times; participate in regular physical exercise increased the riskof suffering from EH0.64(95%CI:0.49~0.84) times compared with not participatein physical exercise; snorers with the risk of EH was1.28(95%CI:1.09~1.51) timescompared with not snorers, and the difference was statistically significant (P <0.05).Much more salt intake is likely to increase the risk of EH of1.20(95%CI:1.04~1.39) times, but eat more coarse grains, vegetables, fruits may reduce the risk of EH.There was significant difference of GLU, UA, TG, TC, HDLC and LDLC levelbetween case group and control group.
With multivariate analysis, BMI≥24kg/m~2, family history of hypertension, shift work, blood glucose, TC/HDLC≥4.5, LDLC≥2.7mmol may increase the risk ofEH of2.09(95%CI:1.59~2.74).1.47(95%CI:1.09~1.966),1.44(95%CI:1.09~1.90),1.45(95%CI:1.04~2.01),2.39(95%CI:1.69~3.38) and2.18(95%CI:1.62~2.95) times separately, and the difference was statistically significant (P <0.05),they were risk factors of EH. Increase intake of fruit, more physical exercise mayreduced the risk of EH, and the OR (95%CI) were0.65(0.49~0.88) and0.74(0.61~0.91), the difference was significant (P <0.05), they were protective factors of EH.
2The relationship between gene polymorphism and essential hypertension
There were significant differences in M235T genotypes and allele frequencies ofAGT gene between cases and control group (χ~2=8.92, P=0.01); the T allele frequencyin case group (62.88%) was higher than control group (57.16%), the difference wassignificant (χ~2=7.16, P=0.01). However, there is not yet that M235T polymorphism ofAGT gene is related with EH (P>0.05) in multivariate analysis.
The II, ID and DD genotype frequency of ACE gene in cases and control groupswere45.99%,39.31%,14.70%and49.81%,40.46%,9.73%separately, and there wasno significant difference of distribution of genotype between case and control groups(χ~2=6.16, P=0.05). The allele frequency of D in case group (34.35%)was higher thancontrol group (29.96%), the difference was significant (χ~2=4.63, P=0.03). Multivariateanalysis revealed that carrying DD genotype increased the risk of EH of1.73(95%CI:1.12~2.68) times, the difference was statistically significant (P <0.05), DD genotypeof ACE gene might be the susceptible genotypes for EH.
There was significant difference in distribution of AA genotype of AT1R genebetween case and control groups(χ~2=5.00, P=0.03). The distribution of alleles A andC was no significant difference between the two groups (P>0.05). Multivariateanalysis showed that the genotype that carrying C allele increase the risk of EH0.55(95%CI:0.35~0.87) times than AA genotype, the difference was statisticallysignificant (P <0.05), which suggesting that A allele may be susceptible gene for EH.
TT, TC and CC genotype frequencies of CYP11B2gene-334T/C loci in case andcontrol groups were50.76%,41.22%,8.02%and49.24%,42.56%,8.20%respectively; carrying T allele and C allele frequencies in case group were71.37%,28.63%, in control group were70.52%,29.48%, there was no significant difference ofgenotype and allele distribution in the two groups (P>0.05), and multivariate analysisconcluded that it can not be considered CYP11B2gene was related with thepathogenesis of EH.
3Analysis of interaction among genes
Stratify analysis method was used to analyze interaction based on the additivemodel among the genes, the results showed that there were negative interactionbetween the AGT gene and ACE gene (χ~2=19.26, P=0.01); There was significantdifference of interactions between AGT gene and CYP11B2gene (χ~2=16.47, P=0.04),between AGT gene and AT1R gene, between ACE gene and AT1R gene. Still, nosignificant interactions based on the additive model between ACE gene and CYP11B2gene, AT1R gene and CYP11B2gene were founded.
After adjusted shift work, BMI, family history of hypertension and other factors,gene variables and their interaction terms were introduced to logistic regression modelfor the multiplicative model of interaction analysis, the results show that there was notinteraction among genes during the development of EH(P>0.05).
4Interaction analysis between gene and shift work
Stratify analysis method was used to analyze interaction based on the additivemodel between shift work and gene, the results showed that there was negativeinteraction between shift work and AGT、ACE、AT1R genes, and the differences weresignificant (P<0.05). Shift work, genetic variables, and the interaction term wereintroduced to logistic regression model, to analyze the relationship of shift work andgene interaction based on the multiplicative model with EH, the interaction OR_(int)values of shift work and AGT、ACE、AT1R、CYP11B2genes were1.05(95%CI:0.70~1.56),0.84(95%CI:0.56~1.25),0.58(95%CI:0.23~1.47),0.81(95%CI:0.52~1.27) separately, there were not statistically significant (P>0.05), still it can notbelieve that there were interactions based on multiplicative model between shift workand each gene.
5Interaction analysis between gene and family history of hypertension
Stratify analysis method was used to analyze interaction based on the additivemodel between family history of hypertension and genes, it found that OR_(int) values ofinteraction terms between family history of hypertension and AGT, AT1R, ACE genewas1.40,1.12,0.71respectively, the difference were significantly (P<0.05); therewas no interactions between family history of hypertension and CYP11B2gene.Logistic regression analysis was used to analyze the interaction between familyhistory and gene based on multiplicative model, it can not believe that there weresignificant difference between family history of hypertension and AGT、ACE、AT1R、 CYP11B2genes.
6Interaction analysis between gene and BMI
Stratify analysis method was used to analyze interaction based on the additivemodel between BMI and genes, it concluded that there were significant difference ininteractions between BMI and AGT, ACE, AT1R, CYP11B2genes(P<0.05). Logisticregression analysis was used to analyze the relationship of interaction between BMIand genes based on multiplicative model, OR_(int)values of interaction terms betweenBMI and AGT、AT1R、CYP11B2were1.11(95%CI:0.75～1.64)、0.66(95%CI:0.27～1.62)、1.29(95%CI:0.84～1.99) respectively, there were no significantdifference in interactions(P>0.05). However, there was interactions between BMIand ACE gene.
7Gene-environment interaction analysis with MDR method
MDR method was used to analyze gene-environment interaction, the resultsshowed that the4-factor and7-factor model were MDR interaction models of gene-environmental factors. There were interactions between shift work and BMI, fruitintake, TC/HDLC, AGT, ACE, CYP11B2gene, which can increase the risk of theincidence of EH.
Conlusions
1Shift work may be risk factor of EH.
2The polymorphism of sequence I/D of ACE gene and A1166C of AT1R gene mightrelated with EH. DD genotype of ACE gene and AA genotype of AT1R gene may besusceptible genotype of EH.
3There were interactions based on additive model between shift work and ACE geneI/D polymorphism, AT1R gene A1166C polymorphism. Still there were interactionsbetween shift work and BMI, fruit intake, TC/HDLC AGT, ACE, of CYP11B2, andwhich could increase the risk of the incidence of EH.
引文
[1]中华人民共和国卫生部.中国居民营养与健康现状[M].2004,10.
[2]中国高血压防治指南修订委员会.中国高血压防治指南(第三版)[M].2010,3.
[3] Hamet P, Pausova Z, Adarichev V, et al. Hypertension: genes and environment[J].J Hypertens.1998,16(4):397-418.
[4]罗雷,栾荣生,袁萍.中国居民高血压主要危险因素的Meta分析[J].中华流行病学杂志.2003,24(1):50-53.
[5]世界卫生组织专家组织报告.高血压的控制[M].1997,6-15.
[6] EliahouHE. Body Weight reductionnecessary to attainnormtensionintheoverweight hypertensive patient[J]. Inter obesity,1981:5(suppll):157.
[7]张庆珍.高血压发病率与体重指数相关性的调查[J].护理杂志.2001,16(3):184.
[8]魏华,郑建东.北京市朝阳门社区高血压流行情况及相关因素调查[J].疾病监测.2001,16(8):310-312.
[9]刘力生,龚兰生.中国高血压防治指南(试行本)[M].北京:卫生部疾病控制司,1999:11.
[10]潘仰中,蔡运昌,刘君实,等.循证医学心血管病临床应用[M].贵阳:贵州省科技出版社,2000,506-507.
[11] Sacks FM, AppelLJ, MooreTJ, et al. Adietaryapproachtopreventhypertension: areview of the Dietary Approaches to Stop Hypertension(DASH) study[J]. Clin Cardiol,1999,22(7):6-10.
[12]赵连成,周北凡,杨军,等.不同人群的食物摄入量与血压水平的关系[J].中国慢性病预防与控制.1996,4(4):155-159.
[13] KatsuyukiMiura, PhilipGreenland, Jeremiah Stamler, et al. Relation of vegetable,fruit, and meat intaketo7-year blood pressurechange in middle-agedmenthechicagowestern electricstudy[J]. American Journalof Epidemiology,2004,159(6):572-580.
[14] Costa. Factors influencing health of workers and tolerance to shift work[J].Theoretical Issues in Ergonomics Science.2003,4(4):263-288.
[15] Grosswald. Shift work on family satisfaction. Families in Society[J]. The Journalof Contemporary Social Services.2004,85(3):413-423.
[16] Kantermann T, Juda M, Merrow M, et al. The human circadian clock’s seasonaladjustment is disrupted by daylight saving time[J]. Curr Biol.2007,17(22):1996-2000.
[17] Folkard S, Tucker P. Shift work, safety and productivity[J]. Occup Med(Lond).2003,53(2):95-101.
[18] Thompson E. Understanding How Night Work Influences the Everyday FamilyLives of Nurses, Their Husbands and Children[M]. Department of Sociology,University of Surrey: Guildford,2009.
[19]钱令嘉.加强我国职业应激研究[J].中华劳动卫生职业病杂志.2003,21(1):1-2.
[20] Rozanski A, Blumenthal JA, Kaplan J. Impact of psychological factors on thepathogenesis of cardiovascular disease and implications for therapy[J]. Circulation.1999,99(16):2192-2217.
[21] Tsigos C, Chrousos GP. Hypothalamic-pituitary-adrenal axis, neuroendocrinefactors and stress[J]. J Psychosom Res.2002,53(4):865-871.
[22] Jun Shigemi, Yoshio Mino, Tadahiro Ohtsu, et al. Effects of perceived job stresson mental health-A longitudinal survey in a Japanese electronics company[J]. Eur JEpidemiol.2000,16(4):371-376.
[23] Eliassonk, Hjemdahlp, Kahant. Cirulatory and Sympahoadrenal responses tostress in borderline and Estadlished hypertension[J]. J Hypertens.1983,1(2):131-139.
[24] Reinhart GA, Lohmeier TE, Hord CE Jr. Hypertension induced by chronic renaladrenergic stimulation is angiotensin dependent[J]. Hypertension.1995,25(5):940-949.
[25] Kouvonen A, Kivim ki M, Elovainio M, et al. Low organisational justice andheavy drinking: a prospective cohort study [J]. Occup Environ Med.2008,65(1):44-50.
[26] Takaki J, Minoura A, Irimajiri H, et al. Interactive effects of job stress and bodymass index on over-eating [J]. J Occup Health.2010,52(1):66-73.
[27]杨艳,余善法,周世义.职业紧张对吸烟饮酒行为影响[J].中国职业医学.2011,38(6):497-499.
[28] Karasek RA, Theorell TG, Schwartz J, et al. Job, psychological factors andcoronary heart disease. Swedish prospective findings and US prevalence findingsusing a new occupational inference method[J]. Adv Cardiol.1982,29:62-67.
[29] Theorell T, Karasek RA. Current issues relating to psychosocial job strain andcardiovascular disease research[J]. J Occup Health Psychol.1996,1(1):9-26.
[30] Peter R, Alfredsson L, Hammar N, et al. High effort, low reward, andcardiovascular risk factors in employed Swedish men and women: baseline resultsfrom the WOLF Study[J]. J Epidemiol Community Health.1998,52(9):540-547.
[31] Peter R, Siegrist J, Hallqvist J, et al. Psychosocial work environment andmyocardial infarction: improving risk estimation by combining two complementaryjob stress models in the SHEEP Study[J]. J Epidemiol Community Health.2002,56(4):294-300.
[32]余善法,李奎荣,杨艳,等.职业紧张与心血管疾病危险因素的关系[J].中华劳动卫生职业病杂志.2003,21(1):12-15.
[33]姚三巧,范雪云,金玉兰,等.职业紧张对职业人群心血管功能的影响[J].中华劳动卫生职业病杂志.2003,21(1):20-22.
[34]刘宝英,张文昌,杨华,等.职业紧张与高血压发病及其与血压值关系的研究[J].中华劳动卫生职业病杂志.2002,20(5):376-380.
[35]任南,刘宝英,张文昌,等.职业紧张因素与高血压发病关系的配对病例对照研究[J].高血压杂志.2001,9(4):345-347.
[36]黄慧玲,刘宝英,任南,等.职业紧张与高血压发病关系的1:2配比病例对照研究[J].中国公共卫生.2002,18(1):11-13.
[37]曲银娥,赵伯阳,范雪云,等.职业紧张与高血压关系探讨[J].工业卫生与职业病.2002,28(4):197-200.
[38]刘宝英,杨华,任南,等.职业紧张在高血压发病中的作用[J].工业卫生与职业病.2005,31(1):22-25.
[39]周权,刘宝英.工作中社会心理行为因素及与原发性高血压关系的研究[J].海峡预防医学杂志.2008,14(2):20-22.
[40]余善法,周文慧,谷桂珍,等.职业紧张和β2-AR基因多态性与高血压关系的病例对照研究[J].工业卫生与职业病.2010,36(2):93-98.
[41] McCubbin JA, Pilcher JJ, Moore DD. Blood pressure increases during asimulated night shift in persons at risk for hypertension[J]. Int J Behav Med.2010,17(4):314-320.
[42] Sfreddo C, Fuchs SC, Merlo AR, Fuchs FD. Shift work is not associated withhigh blood pressure or prevalence of hypertension[J]. PLoS One.2010,5(12):e15250.
[43] Wang XS, Armstrong ME, Cairns BJ, et al. Shift work and chronic disease: theepidemiological evidence[J]. Occup Med (Lond).2011,61(2):78-89.
[44] Niu W, Qi Y, Hou S, et al. Haplotype-based association of the rennin angiotensinaldosterone system genes polymorphisms with essential hypertension among HanChinese: the Fangshan study[J]. J Hypertens.2009,27(7):1384-1391.
[45] Vangjeli C, Clarke N, Quinn U, et al. Confirmation that the renin gene distalenhancer polymorphism REN-5312C/T is associated with increased blood pressure[J].Circ Cardiovasc Genet.2010,3(1):53-59.
[46] Reba M, Kharrat N, Ayadi I, et al. Haplotype structure of five SNPs within theACE gene in the Tunisian population[J]. Ann Hum Biol.2006,33(3):319-329.
[47] Fuentes RM, Notkola IL, Shemeikka S, et al. Familial aggregation of bloodpressure: a population-based family study in eastern Finland[J]. J Hum Hypertens.2000,14(7):441-445.
[48]叶佳颖,钟久昌,高平进,等.肾素血管紧张素系统基因多态性与高血压[J].心血管康复医学杂志.2008,17(6):587-589.
[49] Dickson ME, Sigmund CD. Genetic basis of hypertension: revisitingangiotensinogen[J]. Hypertension.2006,48(1):14-20.
[50] Allen AM. Role of angiotensin in the rostral ventrolateral medulla in thedevelopment and maintenance of hypertension[J]. Curr Opin Pharmacol.2011,11(2):117-123.
[51] Daugherty A, Poduri A, Chen X, et al. Genetic variants of the Renin Angiotensinsystem: effects on atherosclerosis in experimental models and humans[J]. CurrAtheroscler Rep.2010,12(3):167-173.
[52] Jeunemaitre X, Soubrier F, Kotelevtsev YV, et al. Molecular basis of humanhypertension: role of angiotensinogen[J]. Cell.1992,71(1):169-180.
[53] Brand E, Chatelain N, Paillard F, et al. Detection of putative functionalangiotensinogen (AGT) gene variants controlling plasma AGT levels by combinedsegregation-linkage analysis[J]. Eur J Hum Genet.2002,10(11):715-723.
[54] Knox SS, Guo X, Zhang Y, et al. AGT M235T genotype/anxiety interaction andgender in the HyperGEN study[J]. PLoS One.2010,5(10): e13353.
[55] Goldbergova M, Spinarova L, Spinar J, et al. Association of two angiotensinogengene polymorphisms, M235T and G(-6)A, with chronic heart failure[J]. Int J Cardiol.2003,89(2-3):267-272.
[56] F.A. Sayed-Tabatabaei, B.A. Oostra, A. Isaacs, et al. ACE Polymorphisms[J].Circ.Res.2006,98(9):1123-1133.
[57] Rigat B, Hubert C, Alhenc-Gelas F, et al. An insertion/deletion polymorphism inthe angiotensin I-converting enzyme gene accounting for half the variance of serumenzyme levels[J]. J Clin Invest.1990,86(4):1343-1346.
[58] Hilbert P, Lindpaintner K, Beckmann JS, et al. Chromosomal mapping of twogenetic loci associated with blood-pressure regulation in hereditary hypertensiverats[J]. Nature.1991,353(6344):521-529.
[59] Bonnardeaux A, Davies E, Jeunemaitre X, et al. Angiotensin II type1receptorgene polymorphisms in human essential hypertension[J]. Hypertension.1994,24(1):63-69.
[60] Szpirer C, Rivière M, Szpirer J, et al. Chromosomal assignment of human and rathypertension candidate genes: type1angiotensin II receptor genes and the SA gene[J].J Hypertens.1993,11(9):919-925.
[61] Szolnoki Z, Maasz A, Magyari L, et al. The combination of homozygousMTHFR677T and angiotensin II type-1receptor1166C variants confers the risk ofsmall-vessel-associated ischemic stroke[J]. J Mol Neurosci.2007,31(3):201-207.
[62] Brand E, Chatelain N, Mulatero P, et al. Structural analysis and evaluation of thealdosterone synthase gene in hypertension[J]. Hypertension.1998,32(2):198-204．
[63] Johnson AD, GongY, Wang D et al. Promoter polymorphisms in ACE(angiotensin I-converting enzyme) associated with clinical outcomes inhypertension[J]. Clin Pharmacol Ther.2009,85(1):36-44.
[64] Moore N, Dicker P, O'Brien JK, et al. Renin gene polymorphisms and haplotypes,blood pressure, and responses to renin-angiotensin system inhibition[J]. Hypertension.2007,50(2):340-347.
[65] Gormley K, Bevan S, Markus HS. Polymorphisms in genes of therenin-angiotensin system and cerebral small vessel disease[J]. Cerebrovasc Dis.2007,23(2-3):148-155.
[66]曾光.现代流行病学方法与应用[M].北京医科大学中国协和医科大学联合出版社:176-186.
[67]王培桦,沈洪兵,陈峰,等.叉生分析在基因-环境交互作用研究中的应用与意义[J].中华流行病学杂志.2005,26(1):54-57.
[68]夏果,廖芳芳,邹延峰,等.基因与环境交互作用分析方法在复杂疾病研究中的应用[J].中国卫生统计.2009,26(1):87-90.
[69]张军,于石成,杨功焕,等.遗传易感性-环境交互作用研究方法进展[J].预防医学论坛.2010,16(1):58-62.
[70]柏建岭,荀鹏程,赵杨,等.不完全病例对照研究基因环境交互作用的估计[J].中华流行病学杂志.2006,27(1):72-75.
[71]骆常好,刘桂芬,张爱莲.多因子降维法和Logistic回归交互效应分析对比研究[J].中国药物与临床.2008,8(10):777-779.
[72]赵自强,郑明.应用分类树模型筛选logistic回归中的交互因素[J].中国卫生统计.2007,24(2):114-116.
[73] Ritchie MD, Hahn Lw, Rodi N, et al. Multifactor dimensionality reductionreveals high-order interactions among estrogen-metabolism genes in sporadic breastcancer[J]. Am J Hum Genet.2001,69(1):138-147.
[74]唐迅,李娜,胡永华.应用多因子降维法分析基因基因交互作用[J].中华流行病学杂志.2006,27(5):437-441．
[75] Williams SM, Ritchie MD, Phillips JA, et a1. Multilocus analysis of hypertension:a hierarchical approach[J]. Hum Hered.2004,57(1):28-38．
[76] Brennan P. Gene-environment interaction and aetiology of cancer: what does itmean and how can we measure it[J]? Carcinogenesis.2002,23(3):381-387.
[77]王忠旭,秦汝莉,李玉珍,等.我国23家煤矿企业职业病危害因素及其防护现状[J].环境与职业医学.2009,26(6):565-568.
[78]王雪涛,马骏,关砚生,等.我国地方煤矿职业危害现状调查报告[J].中国安全生产科学技术.2008,4(1):91-94.
[79]范雪云,李庆友,白玉萍,等.煤矿工人职业性多发病研究[J].中华预防医学杂志.1996,30(5):319.
[80]秦天榜.煤矿井下工人高血压患病情况标化分析[J].职业卫生与病伤.1997,12(4):206-207.
[81]梅仁彪,孙桂明,徐展,等.井下作业对高血压矿工血浆皮质醇水平的影响[J].中国行为医学科学.2000,9(1):31-33.
[82]梅仁彪,孙桂明.煤矿井下作业与井下矿工高血压病相关性研究[J].中国工业医学杂志.2001,13(5):299-301.
[83]梅仁彪,孙桂明,徐广绪.煤矿井下作业对高血压矿工血浆血管紧张素II水平的影响[J].中国工业医学杂志.2001,14(5):288-289.
[84]张玉玲,马兰,马铭良.煤矿接尘职工高血压患病情况调查[J].工业卫生与职业病.2001,27(5):285-286.
[85]梅仁彪.高血压矿工血浆肾素、血管紧张素II、醛固酮和皮质醇水平的分析[J].中国工业医学杂志[J].2004,17(4):220-223.
[86]郑国华,李玉,李红,等.煤矿职工原发性高血压及其影响因素分析[J].中国公共卫生.2004,20(6):744-745.
[87]石长胜.煤矿工人高血压危险因素流行病学调查[J].中国职业医学.2007,34(5):439-450.
[88]曹宏,索霞,黄建军.煤矿职工高血压发病危险因素调查[J].职业与健康.2009,25(4):344-346.
[89]王彩云,赵辉.2009年某煤矿40岁以上职工体检结果分析[J].预防医学.2010,48(24):69-70.
[90]王学东,张廷久,等.阜新矿区男性矿工高血压及其危险因素分析[J].中国临床研究.2010,23(5):437-438.
[91]张卫清,信雅菊.煤矿工人高血压状况调查分析[J].中国疗养医学.2011,20(12):1127-1128.
[92]世界卫生组织专家组织报告.高血压的控制[M].北京:人民卫生出版社.1997,6-15.
[93] EliahouHE. Body Weight reductionneces sary to attainnormtensionintheoverweight hypertensive patient[J]. Inter obesity,1981:5(suppll):157.
[94]张庆珍.高血压发病率与体重指数相关性的调查[J].护理杂志.2001,16(3):184.
[95]魏华,郑建东.北京市朝阳门社区高血压流行情况及相关因素调查[J].疾病监测.2001,16(8):310-312.
[96] Pi-Sunyer FX. The epidemiology of central fat distribution in relation todisease[J]. Nutr Rev.2004,62(7Pt2): S120-126.
[97]罗雷,栾荣生,袁萍.中国居民高血压主要危险因素的Meta分析[J].中华流行病学杂志.2003,24(1):50-53.
[98]刘红艳,彭辉,刘奥博,等.中国人原发性高血压危险因素Meat分析[J].中国心血管杂志.2009,14(3):205-209.
[99] KatsuyukiMiura, PhilipGreenland, Jeremiah Stamler, et al. Relation of vegetable,fruit, and meat intaketo7-year blood pressurechange in middle-agedmenthechicagowestern electricstudy[J]. American Journalof Epidemiology,2004,159(6):572-580.
[100]赵文华,王军波,肖颖,等.膳食及营养因素对农村居民高血压患病影响的多因素分析[J].营养学报.2002,24(3):274-277.
[101] Wildman RP, Gu D, Muntner P, et al. Alcohol intakeandhyperten-sion subtypesin Chinese men[J]. Journalof Hypertension.2005,23(4):737-743.
[102]李军昕,张波.不同年代中国人群高血压病危险因素的Meta分析[J].中国循证医学杂志.2009,9(12):1302-1309.
[103] Rhee MY, Na SH, Kim YK, et al. Acute effects of cigarette smoking on arterialstiffness and blood pressure in male smokers with hypertension[J]. Am J Hypertens.2007,20(6):637-641.
[104]杨波,邱泉,栾玉明,等.海珠区4062名男性常住居民吸烟指数对高血压影响分析[J].现代预防医学.2010,37(8):1553-1555.
[105] Partinen M, Palom ki H. Snoring and cerebral infarction[J]. Lancet.1985,2(8468):1325-1326.
[106]徐宝珠.打鼾与脑血管疾病关系的调查[J].中国慢性病预防与控制.1999,7(l):22.
[107]马金香,孙业桓,曹多志,等.男性打鼾与高血压的关系[J].中国慢性病预防与控制.2005,13(2):60-63.
[108] Chearskul S, Charoenlarp K, Thongtang V, et al. Study of plasma hormones andlipids in healthy elderly Thais compared to patients with chronic diseases: diabetesmellitus, essential hypertension and coronary heart disease[J]. J Med Assoc Thai.2000,83(3):266-277.
[109] Ridker PM. High-sensitivity C-reactive protein: potential adjunct for global riskassessment in the primary prevention of cardiovascular disease[J]. Circulation.2001,103(13):1813-1818.
[110]李莹,陈志红,周北凡,等.我国中年人群血清TC/HDLC比值与缺血性和出血性脑卒中发病危险性[J].中华神经科杂志.2005,38(5):305-308.
[111] Sfreddo C, Fuchs SC, Merlo AR, Fuchs FD. Shift work is not associated withhigh blood pressure or prevalence of hypertension[J]. PLoS One.2010,5(12):e15250.
[112] McCubbin JA, Pilcher JJ, Moore DD. Blood pressure increases during asimulated night shift in persons at risk for hypertension[J]. Int J Behav Med.2010,17(4):314-320.
[113]石长胜.煤矿工人高血压危险因素流行病学调查[J].中国职业医学.2007,34(5):439-440.
[114]阎进德,姚三巧,白玉萍,等.职业紧张对长途客车司机血压的影响[J].工业卫生与职业病.2000,26(3):134-136.
[115]刘静波,张幼辰,俞顺章.血管紧张素原基因多态性与原发性高血压关系的研究[J].中华流行病学杂志.2000,21(6):407-409.
[116] Nishiuma S, Kario K, Kayaba K, et al. Effect of the angiotensinogen geneMet235-The variant on blood pressure and other cardiovascular risk factors in twoJapanses populations[J]. J Hypertens.1995,13(7):717-722.
[117] Knox SS, Guo X, Zhang Y, et al. AGT M235T genotype/anxiety interaction andgender in the HyperGEN study[J]. PLoS One.2010,5(10): e13353.
[118] Goldbergova M, Spinarova L, Spinar J, et al. Association of twoangiotensinogen gene polymorphisms, M235T and G(-6)A, with chronic heartfailure[J]. Int J Cardiol.2003,89(2-3):267-72.
[119] Ortlepp JR, Metrikat J, Mevissen V, et al. Relation between the angiotensinogen(AGT) M235T gene polymorphism and blood pressure in a large, homogeneous studypopulation[J]. J Hum Hypertens.2003,17(8):555-559.
[120] Mondry A, Loh M, Liu P, et al. Polymorphisms of the insertion/deletion ACEand M235T AGT genes and hypertension: surprising new findings and meta-analysisof data. BMC Nephrol.2005,11(6):1-2.
[121] F.A. Sayed-Tabatabaei, B.A. Oostra, A. Isaacs, et al. ACE Polymorphisms[J].Circ.Res.2006,98(9):1123-1133.
[122] Rigat B, Hubert C, Alhenc-Gelas F, et al. An insertion/deletion polymorphism inthe angiotensin I-converting enzyme gene accounting for half the variance of serumenzyme levels[J]. J Clin Invest.1990,86(4):1343-1346.
[123] Hilbert P, Lindpaintner K, Beckmann JS, et al. Chromosomal mapping of twogenetic loci associated with blood-pressure regulation in hereditary hypertensiverats[J]. Nature.1991,353(6344):521-529.
[124] Gunes HV, Ata N, Degirmenci I, et al. Frequency of angiotensin-convertingenzyme gene polymorphism in Turkish hypertensive patients[J]. Int J Clin Pract.2004,58(9):838-843.
[125] Stefansson B, Ricksten A, Rymo L, et al. Angiotensin-converting enzyme geneI/D polymorphism in malignant hypertension[J]. Blood Press.2000,9(2-3):104-109.
[126] Rigat B，Hubert C，Corvol P，et a1．PCR detection of the insertion／deletionpolymorphism of the human angiotensin converting enzyme gene(DCPl)[J]．NucleicAcids Res.1992,20(6):1433．
[127]李娜，郭淑霞，张翼华，等.哈萨克族高血压与血管紧张素转换酶基因多态性[J].中国公共卫生,2008,24(3):274-275.
[128] Ned RM, Yesupriya A, Imperatore G, et al. The ACE I/D Polymorphism in USAdults: Limited Evidence of Association With Hypertension-Related Traits andSex-Specific Effects by Race/Ethnicity[J]. Am J Hypertens.2011,13. doi:10.1038/ajh.2011.182.
[129] Yanyan L. The angiotensin converting enzyme gene insertion/deletion (I/D)polymorphism and essential hypertension in the Chinese population: a meta-analysisincluding21058participants[J]. Intern Med J.2011,1. doi:10.1111/j.1445-5994.2011.02584.x.
[130]张琦,沈志霞,李宏芬,等.血管紧张素转换酶基因插入/缺失多态性在人群中的分布及其与原发性高血压的关系[J].中华医学遗传学杂志.2003,20(5):438-440.
[131]李宏芬,沈志霞,常延河,等.中国人群血管紧张素转换酶基因与血管紧张素Ⅱ21型受体基因A1166C单核苷酸多态性分析[J].中华检验医学杂志,2003,26(2):89-92.
[132]刘丽娟,佟伟军,张永红,等.蒙古族ACE基因多态性与高血压关系的研究[J].中国公共卫生.2003,19(4):392-393.
[133] Szpirer C, Rivière M, Szpirer J, et al. Chromosomal assignment of human andrat hypertension candidate genes: type1angiotensin II receptor genes and the SAgene[J]. J Hypertens.1993,11(9):919-925.
[134] Kobashi G, Hata A, Ohta K, et al. A1166C variant of angiotensin II type1receptor gene is associated with severe hypertension in pregnancy independently ofT235variant of angiotensinogen gene[J]. J Hum Genet.2004,49(4):182-186.
[135] Sugimoto K, Katsuya T, Ohkubo T, et al. Association between angiotensin IItype1receptor genepolymorphismandessential hypertension: the Ohasama Study[J].Hypertens Res.2004,27(8):551-556.
[136]徐欣,杨承健,郑义通,等.血管紧张素II-1型受体基因A1166C多态性与高血压的相关研究初探[J].中国微循环.2009,13(1):49-52.
[137]左彦方,龙爱梅.血管紧张素II1型受体基因A1166C多态性与原发性高血压易感性的Meat分析[J].循证医学.2008,8(6):349-352.
[138] Niu W, Qi Y. Association of the angiotensin II type I receptor gene+1166A>Cpolymorphism with hypertension risk: evidence from a meta-analysis of16474subjects[J]. Hypertens Res.2010,33(11):1137-1143.
[139] Palatini P, Ceolotto G, Dorigatti F, et al. Angiotensin II type1receptor genepolymorphism predicts development of hypertension and metabolic syndrome[J]. AmJ Hypertens.2009,22(2):208-214.
[140] Brand E, Chatelain N, Mulatero P, et al. Structural analysis and evaluation ofthe aldosterone synthase gene in hypertension[J]. Hypertension,1998,32:198-204．
[141] Sookoian S, Gianotti TF, González CD, et al. Association of the C-344Taldosterone synthase gene variant with essential hypertension: a meta-analysis[J]. JHypertens.2007,25(1):5-13.
[142] Hlubocká Z, Jáchymová M, Heller S, et al. Association of the-344T/Caldosterone synthase gene variant with essential hypertension[J]. Physiol Res.2009,58(6):785-792.
[143] Sun X, Yang J, Hou X, et al. Relationship between-344T/C polymorphism inthe aldosterone synthase gene and atrial fibrillation in patients with essentialhypertension[J]. J Renin Angiotensin Aldosterone Syst.2011,12(4):557-563.
[144] NIU WQ, WANG JB, LI SJ, et al. Relationship between Aldosterone Synthasegene (CYP11B2) Polymorphisms and Essential Hypertension in a Northern ChineseHan Population[J]. Acta Acad Med Sin.2007,29(3):329-335.
[145]徐新娟,汪师贞,林仁勇,等.新疆哈萨克族隔离群醛固酮合成酶基因多态性与原发性高血压的关联性[J].中华医学遗传学杂志.2004,21(6):622-624.
[146]李庆祥,张宇清,靳凤艳,等.醛固酮合成酶(CYP11B2)基因T(-344)C多态性与高血压病相关性研究[J].高血压杂志.2003,11(3):238-240.
[147] Tsujita Y, Iwai N, Katsuya T, et al. Lack of association between geneticpolymorphism of CYP11B2and hypertension in Japanese: the Suita Study[J].Hypertens Res.2001,24(2):105-109.
[148] Alvarez-Madrazo S, Connell JM, Freel EM. Role of genetic variation inregulation of aldosterone biosynthesis[J]. Endocr Dev.2011,20:106-115.
[149] Cheng X, Xu G. A systemic review of the relationship between aldosteronesynthase-344C/T polymorphism and hypertension in Han[J]. Clin Exp Hypertens.2010,32(5):301-307.
1Costa. Factors influencing health of workers and tolerance to shift work. TheoreticalIssues in Ergonomics Science.2003,4(4),263-288.
2Grosswald. Shift work on family satisfaction. Families in Society: The Journal ofContemporary Social Services.2004,85(3),413-423.
3Anders Knutsson. Methodological Aspects of Shift-Work Research. ChronobiologyInternational.2004,21(6):889-897.
4Akerstedt T. Shift work and disturbed sleep/wakefulness. Occup Med(Lond).2003,53(2):89-94.
5Roenneberg T, Kuehnle T, Juda M, et al. Epidemiology of the human circadianclock. Sleep Med. Rev.2007,11(6):429-438.
6Kantermann T, Juda M, Merrow M, et al. The human circadian clock’s seasonaladjustment is dis-rupted by daylight saving time. Curr Biol.2007,17(22):1996-2000.
7Baker D. The use and health consequences of shift work. Int J Health Serv.1980,10(3):405-420.
8Folkard S, Tucker P. Shift work, safety and productivity. Occup Med(Lond).2003,53(2):5-101.
9Foster RG, Wulff K. The rhythm of rest and excess. Nat Rev Neurosci.2005,6(5):407-414.
10Haus E, Smolensky M. Biological clocks and shift work: circadian dysregulationand potential long-term effects. Cancer Causes Control.2006,17(4):489-500.
11Knutsson A. Health disorders of shift workers. Occup Med(Lond).2003,53(2):103-108.
12Whitehead DC, Thomas H, Jr, Slapper DR. A rational approach to shift work inemergency medicine. Ann Emerg Med.1992,21(10):1250-1258.
13Thompson E.Understanding How Night Work Influences the Everyday FamilyLives of Nurses, Their Husbands and Children. Department of Sociology, Universityof Surrey: Guildford,2009.
14Santhi N, Aeschbach D, Horowitz TS, et al. The impact of sleep timing and brightlight xposure on attentional impairment during night work. J Biol Rhythms,2008,23(4):341-52.
15Sudo N, Ohtsuka R. Fatigue complaints among female shift workers in a computerfactory of Japan. J Hum Ergol (Tokyo).2002,31(1-2):41-51.
16Akerstedt T, Knutsson A, Westerholm P, et al. Mental fatigue, work and sleep. JPsychosom Res.2004,57(5):427-433.
17Jianhua SHEN, Leigh C.P. Botly, Sharon A.Chung, et al. Fatigue and shift work.J.Sleep RES.2006(15):1-5.
18Hossain J L, Reinish L W, Kayumov, et al. Underlying sleep pathology may causechronic high fatigue in shift-workers. Sleep Res.2003(12):223-230.
19Zhen Lu W, Ann Gwee K, Yu Ho K. Functional bowel disorders in rotating shiftnurses may be related to sleep disturbances. Eur J Gastroenterol Hepatol.2006,18(6):623-627.
20Geiger Brown J, Rogers VE, Trinkoff AM, et al. Sleep, sleepiness, fatigue, andperformance of12-hour-shift nurses. Chronobiol Int.2012,29(2):211-219.
21Parshuram CS, To T, Seto W, et al. Systematic evaluation of errors occurringduring the preparation of intravenous medication. Can Med Assoc J.2008,178(1):42–48.
22Fisman DN, Harris AD, Rubin M, et al. Fatigue increases the risk of injury fromsharp devices in medical trainees: Results from a case-crossover study. Infect ControlHosp Epidemiol.2007,28(1):10-17.
23Baker K, Olson J, Morisseau D. Work practices, fatigue, and nuclear power plantsafety performance. Hum Factors.1994,36(2):244-257.
24Mulgrew AT, Ryan CF, Fleetham JA, et al. The impact of obstructive sleep apneaand daytime sleepiness on work limitation. Sleep Med.2007,9(1):42-53.
25Moller HJ, Kayumov L, Bulmash EL, et al. Simulator performance, microsleepepisodes, and subjec-tive sleepiness: Normative data using convergentmethod-ologies to assess driver drowsiness. J Psychosom Res.2006,61(3):335-342.
26De Pinho RS, da Silva-Junior FP, Bastos JP, et al. Hypersomnolence and accidentsin truck drivers: A cross-sectional study. Chronobiol Int.2006(23):963-971.
27Van Amelsvoort LG, Jansen NW, Swaen GM, et al. Direction of shift rotationamong three-shift workers in relation to psychological health and work-familyconflict. Scand J Work Environ Health.2004,30(2):149-156.
28Hossain NK, Irvine J, Ritvo P, et al. Evaluation and treatment of sleep complaints:Patients’subjective responses. Psychother Psychosom.2007,76(6):395-399.
29Shapiro CM, Auch C, Reimer M, et al. A new approach to the construct ofalertness. J Psychosom Res.2006,60(6):595-603.
30B ggild H, Knutsson A. Shift work, risk factors and cardiovascular disease. ScandJ Work Environ Health.1999,25(2):85-99.
31Frost P, Kolstad HA, Bonde JP. Shift work and the risk of ischemic heart disease-asystematic review of the epidemiologic evidence. Scand J Work Environ Health.2009,35(3):163-79.
32Puttonen S, Kivim ki M, Elovainio M, et al. Shift work in young adults andcarotid artery intima-media thickness: The Cardiovascular Risk in Young Finns study.Atherosclerosis.2009,205(2):608-613.
33Fujino Y, Iso H, Tamakoshi A, et al. A prospective cohort study of shift work andrisk of ischemic heart disease in Japanese male workers. Am J Epidemiol.2006,164(2):128-135.
34Yadegarfar G, McNamee R. Shift work, confounding and death from ischaemicheart disease. Occup Environ Med.2008,65(3):158-163.
35Radi S, Ostry A, Lamontagne AD. Job stress and other working conditions:relationships with smoking behaviors in a representative sample of workingAustralians. Am J Ind Med.2007,50(8):584-596.
36Van Amelsvoort LG, Jansen NW, Kant I. Smoking among shift workers: more thana confounding factor. Chronobiol Int.2006,23(6):1105-1113.
37Nabe-Nielsen K, Garde AH, Tüchsen F, et al. Cardiovascular risk factors andprimary selection into shift work. Scand J Work Environ Health.2008,34(3):206-212.
38Lennern s M, Hambraeus L, kerstedt T. Shift related dietary intake in day andshift workers. Appetite.1995,25(3):253-265.
39Morikawa Y, Miura K, Sasaki S, et al. Evaluation of the effects of shift work onnutrient intake: a cross-sectional study. J Occup Health.2008,50(3):270-78.
40Biggi N, Consonni D, Galluzzo V, et al. Metabolic syndrome in permanent nightworkers. Chronobiol Int.2008,25(2):443-454.
41Dochi M, Suwazono Y, Sakata K, et al. Shift work is a risk factor for increasedtotal cholesterol level: a14-year prospective cohort study in6886male workers.Occup Environ Med.2009,66(9):592-597.
42Morikawa Y, Nakagawa H, Miura K, et al. Effect of shift work on body mass indexand metabolic parameters. Scand J Work Environ Health.2007,33(1):45-50.
43Ghiasvand M, Heshmat R, Golpira R, et al. Shift working and risk of lipiddisorders: a cross-sectional study. Lipids Health Dis.2006,10(4):5-9.
44Sookoian S, Gemma C, Fernandez Gianotti T, et al. Effects of rotating shift workon biomarkers of metabolic syndrome and inflammation. J Intern Med.2007,261(3):285-292.
45Cappuccio FP, Taggart FM, Kandala NB, et al. Meta-analysis of short sleepduration and obesity in children and adults. Sleep.2008,31(5):619-626.
46Marshall NS, Glozier N, Grunstein RR. Is sleep duration related to obesity? acritical review of the epidemiological evidence. Sleep Med Rev.2008,12(4):289-298.
47Suwazono Y, Dochi M, Sakata K, et al. A longitudinal study on the effect of shiftwork on weight gain in male Japanese workers. Obesity (Silver Spring).2008,16(8):1887-1893.
48Karasek RA, Theorell T. Healthy work: stress, productivity, and the reconstructionof working life. New York (NY): Basic Books,1990.
49Ala-Mursula L, Vahtera J, Pentti J, et al. Effect of employee worktime control onhealth: a prospective cohort study. Occup Environ Med.2004,61(3):254-261.
50Ala-Mursula L, Vahtera J, Kivim ki M, et al. Employee control over workingtimes: associations with subjective health and sickness absences. J EpidemiolCommunity Health.2002,56(4):272-278.
51Siegrist J, Peter R, Junge A, et al. Low status control, high effort at work andischemic heart disease: prospective evidence from blue-collar men. Soc Sci Med.1990,31(10):1127-1134.
52Peter R, Alfredsson L, Knutsson A, et al. Does a stressful psychosocial workenvironment mediate the effects of shift work on cardiovascular risk factors? Scand JWork Environ Health.1999,25(4):376-81.
53Albertsen K, Rafnsdóttir G, Grimsmo A, et al. Workhours and worklife balance.SJWEH Suppl.2008,(5):14-21.
54Costa G, Sartori S, kerstedt T. Influence of flexibility and variability of workinghours on health and well-being. Chronobiol Int.2006,23(6):1125-1137.
55Alberti KG, Eckel RH, Grundy SM, et al. Harmonizing the metabolic syndrome: ajoint interim statement of the In-ternational Diabetes Federation Task Force onEpidemiology and Prevention; National Heart, Lung, and Blood Institute; AmericanHeart Association; World Heart Feder-ation; International Atherosclerosis Society;and Interna-tional Association for the Study of Obesity. Circulation.2009,120(16):1640-1645.
56Galassi A, Reynolds K, He J. Metabolic syndrome and risk of cardiovasculardisease: a meta-analysis. Am J Med.2006,119(10):812-819.
57Karlsson B, Knutsson A, Lindahl B. Is there an association between shift work andhaving a metabolic syndrome? Results from a population based study of27,485people. Occup Environ Med.2001,58(11):747-752.
58Lin YC, Hsiao TJ, Chen PC. Persistent rotating shift-work exposure acceleratesdevelopment of metabolic syndrome among middle-aged female employees: afive-year follow-up. Chronobiol Int2009,26(4):740-755.
59Lin YC, Hsiao TJ, Chen PC. Shift work aggravates metabolic syndromedevelopment among early-middle-aged males with elevated ALT. Wor ld JGastroenterol.2009,15(45):5654-5661.
60De Bacquer D, Van Risseghem M, Clays E, et al. Rotating shift work and themet-abolic syndrome: a prospective study. Int J Epidemiol.2009,38(3):848-854.
61Sookoian S, Gemma C, Gianotti TF, et al. Effects of rotating shift work onbiomarkers of metabolic syndrome and inflammation. J Int Med.2007,261(3):285-292.
62Pietroiusti A, Neri A, Somma G, et al. Incidence of metabolic syndrome amongnight shift health care workers. Occup Environ Med.2010,67(1):54-57.
63Esquirol Y, Bongard V, Mabile L, et al. Shift work and metabolic syndrome:respective impacts of job strain, physical activity, and dietary rhythms. Chronobiol IntJ Biol Med Rhythm Res.2009,26(3):544-559.
64Mikuni E, Ohoshi T, Hayashi K, et al. Glucose intolerance in an employedpopulation. Tohoku J Exp Med.1983,141(Suppl):251-256.
65Kawakami N, Araki S, Takatsuka N, et al. Overtime, psychosocial workingconditions, and occurrence of non-insulin dependent diabetes mellitus in Japanesemen. J Epidemiol Commun Health.1999,53(6):359-363.
66Nagaya T, Yoshida H, Takahashi H, et al. Markers of insulin resistance in day andshift workers aged30-59years. Int Arch Occup Environ Health.2002,75(8):562-568.
67Morikawa Y, Nakagawa H, Miura K, et al. Shift work and the risk of diabetesmellitus among Japanese male factory work-ers. Scand J Work Environ Health.2005,31(3):179-183.
68Karlsson B, Alfredsson L, Knutsson A, et al. Total mortality and cause-specificmortality of Swedish shift-and dayworkers in the pulp and paper indus-try in1952-2001. Scand J Work Environ Health2005,31(1):30-35.
69Kroenke CH, Spiegelman D, Manson J, et al. Work characteristics and incidence oftype2diabetes in women. Am J Epidemiol.2007,165(2):175-183.
70Pan A, Schernhammer ES, Sun Q, et al. Rotating night shift work and risk of type2diabetes: two prospective cohort studies in women. PLoS Med.2011,8(12):e1001141.
71Akerstedt T, Knutsson A, Alfredsson L, et al. Shift work and cardiovascular disease.Scand J Work Environ Health.1984,10(6):409-414.
72Knutsson A, Akerstedt T, Jonsson BG, et al. Increased risk of ischaemic heartdisease in shift workers. Lan-cet.1986,2(8498):89-92.
73Kristensen TS. Cardiovascular diseases and the work environment. A criticalreview of the epidemiologic literature on nonchemical factors. Scand J Work EnvironHealth.1989,15(3):165-179.
74Boggild H, Knutsson A. Shift work, risk factors and cardio-vascular disease. ScandJ Work Environ Health.1999,25(2):85-99.
75Haupt CM, Alte D, Do¨rr M, et al. The relation of exposure to shift work withatherosclerosis and myocardial infarction in a general population. Atherosclerosis.2008,201(1):205-211.
76Ellingsen T, Bener A, Gehani AA. Study of shift work and risk of coronary events.J R Soc Promot Health.2007,127(6):265-267.
77Hermansson J, Gillander Gadin K, Karlsson B, et al. Ischemic stroke and shiftwork. Scand J Work Environ Health.2007,33(6):435-439.
78Brown DL, Feskanich D, Sa′nchez BN, et al. Rotating night shift work and therisk of ischemic stroke. Am J Epidemiol.2009,169(11):1370-1377.
79Puttonen S, Ha¨ rma¨ M, Hublin C. Shiftwork and cardiovascular disease-pathways from circadian stress to morbidity. Scand J Work Environ Health.2010,36(2):96-108.
80Hansson GK. Inflammation, atherosclerosis, and coronary artery disease. N Engl JMed.2005,352(16):1685-1695.
81Okamoto H, Tsunoda T, Teruya K, et al. An occupational health study ofemergency physicians in Japan: health assessment by immune variables(CD4, CD8,CD56, and NK cell activity) at the beginning of work. J Occup Health.2008,50(2):136-146.
82Copertaro A, Bracci M, Barbaresi M, et al. Assessment of cardiovascular risk inshift healthcare workers. Eur J Cardiovasc Prev Rehabil.2008,15(2):224-229.
83Martins PJ, D’Almeida V, Vergani N, et al. Increased plasma homocysteine levelsin shift working bus drivers. Occup Environ Med.2003,60(9):662-666.
84Lavie L, Lavie P. Elevated plasma homocysteine in older shift-workers: a potentialrisk factor for cardiovascular morbidity. Chronobiol Int.2007,24(1):115-128.
85Antoniades C, Antonopoulos AS, Tousoulis D, et al. Homocysteine and coronaryatherosclerosis: from folate fortification to the recent clinical trials. Eur Heart J.2009,30(1):6-15.
86McCully KS. Chemical pathology of homocysteine, IV: excitotoxicity, oxidativestress, endothelial dysfunction, and inflammation. Ann Clin Lab Sci.2009,39(3):219-232.
87Amir O, Alroy S, Schliamser JE, et al. Brachial artery endothelial function inresidents and fellows working night shifts. Am J Cardiol.2004,93(7):947-949.
88Haupt CM, Alte D, Dorr M, et al. The relation of exposure to shift work withatherosclerosis and myocardial infarction in a general population. Atherosclerosis.2008,201(1):205-211.
89Puttonen S, Kivim ki M, Elovainio M, et al. Shift work in young adults andcarotid artery intima-media thickness: The Cardiovascular Risk in Young Finns study.Atherosclerosis.2009,205(2):608-613.
90Chung MH, Kuo TB, Hsu N, et al. Sleep and autonomic nervous system changesenhanced cardiac sympathetic modulations during sleep in permanent night shiftnurses. Scand J Work Environ Health.2009,35(3):180-187.
91Furlan R, Barbic F, Piazza S, et al. Modifications of ardiac autonomic profileassociated with a shift schedule of work. Circulation.2000,102(16):1912-1916.
92Ohira T, Tanigawa T, Iso H, et al. Effects of shift work on24-hour ambulatoryblood pressure and its variability among Japanese workers. Scand J Work EnvironHealth.2000,26(5):421-426.
93Suwazono Y, Dochi M, Sakata K, et al. Shift work is a risk factor for increasedblood pressure in Japanese men: a14-year historical cohort study. Hypertension.2008,52(3):581-586.
94Lo SH, Liau CS, Hwang JS, et al. Dynamic blood pressure changes and recoveryunder different work shifts in young women. Am J Hypertens.2008,21(7):759-764.
95Virkkunen H, H rm M, Kauppinen T, et al. Shift work, occupational noise andhysical workload with ensuing development of blood pressure and their joint effect onthe risk of coronary heart disease. Scand J Work Environ Health.2007,33(6):425-434.
96Sfreddo C, Fuchs SC, Merlo A′R, et al. Shift work is not associated with highblood pressure or prevalence of hypertension. PLoS ONE5(12): e15250.doi:10.1371/journal.pone.0015250.
97Preetha Anand, Ajaikumar B, Kunnumakara, et al. Cancer is a Preventable Diseasethat Requires Major Lifestyle Changes. Pharm Res.2008,25(9):2097-2116.
98Straif K, Baan R, Grosse Y, et al. Carcinogenicity of shift work, painting, andfire-fighting. Lancet Oncol.2007,8(12):1065-1066.
99Megdal SP, Kroenke CH, Laden F, et al. Night work and breast cancer risk: asystematic review and meta-analysis. Eur J Cancer.2005,41(13):2023-2032.
100Kolstad HA. Nightshift work and risk of breast cancer and other cancers: Acritical review of the epidemiologic evidence. Scand J Work Environ Health.2008,34(1):5-22.
101Kubo T, Ozasa K, Mikami K, et al. Prospective cohort study of the risk ofprostate cancer among rotating shift workers: findings from the Japan CollaborativeCohort Study. Am J Epidemiol.2006,164(6):549-555.
102Conlon M, Lightfoot N, Kreiger N. Rotating shift work and risk of prostatecancer. Epidemiology.2007,18(1):182-183.
103Schernhammer ES, Laden F, Speizer FE, et al. Night-shift work and risk ofcolorectal cancer in the Nurses’ Health Study. J Natl Cancer Inst.2003,95(11):825-828.
104Schwartzbaum J, Ahlbom A, Feychting M. Cohort study of cancer risk amongmale and female shift workers. Scand J Work Environ Health.2007,33(5):336-343.
105Tynes T, Hannevik M, Andersen A, et al. Incidence of breast cancer in Norwegianfe-male radio and telegraph operators. Cancer Causes Control.1996,7(2):197-204.
106Lahti TA, Partonen T, Kyyro¨ nen P, et al. Night-time work predisposes tonon-Hodgkin lymphoma. Int J Cancer.2008,123(9):2148-2151.
[1] Tamaki S, Iwai N, Tsujita Y, et al. Genetic polymorphism of CYP11B2gene andhypertension in Japanese[J]. Hypertension.1999,33:266-270.
[2]梅仁彪,孙桂明.煤矿井下作业与井下矿工高血压病相关性研究[J].中国工业医学杂志.2000,13(5):299-301.
[3] Komiya I et al. Lys(173)Arg and344T/C variants of CYP11B2in Japanesepatients with low-renin hyper-tension[J]. Hypertension2000,35:699-703.
[4] Brand E, Chatelain N, Mulatero P, et al. Structural analysis and evaluation of thealdosterone synthase gene in hypertension[J]. Hypertension.1998,32:198-204．
[5] Sookoian S, Gianotti TF, González CD, et al. Association of the C-344Taldosterone synthase gene variant with essential hypertension: a meta-analysis[J]. JHypertens.2007,25(1):5-13.
[6] Hlubocká Z, Jáchymová M, Heller S, Umnerová V, et al. Association of the-344T/C aldosterone synthase gene variant with essential hypertension[J]. Physiol Res.2009,58(6):785-792.
[7] Sun X, Yang J, Hou X, et al. Relationship between-344T/C polymorphism in thealdosterone synthase gene and atrial fibrillation in patients with essentialhypertension[J]. J Renin Angiotensin Aldosterone Syst.2011,12(4):557-563.
[8]李庆祥,张宇清,靳凤艳等.醛固酮合成酶（CYP11B2）基因T(-344)C多态性与高血压病相关性研究[J].高血压杂志.2003,11(3):238-240.
[9] Tsujita Y, Iwai N, Katsuya T, et al. Lack of association between geneticpolymorphism of CYP11B2and hypertension in Japanese: the Suita Study[J].Hypertens Res.2001,24(2):105-109.
[10] NIU Wen-quan, WANG Jiang-bing, LI Su-jie, et al. Relationship betweenAldosterone Synthase gene (CYP11B2) Polymorphisms and Essential Hypertensionin a Northern Chinese Han Population[J]. Acta Acad Med Sin.2007,29(3):329-335.
[11] Kumar NN, Benjafield AV, Lin RCY, et al. Haplotype analysis of aldosteronesynthase gene (CYP11B2) polymorphism shows association with essentialhypertension[J]. J Hypertens.2003,21:1331-1337.
[2]中国高血压防治指南修订委员会.中国高血压防治指南(第三版)[M].2010,3.
[3] Hamet P, Pausova Z, Adarichev V, et al. Hypertension: genes and environment[J].J Hypertens.1998,16(4):397-418.
[4]罗雷,栾荣生,袁萍.中国居民高血压主要危险因素的Meta分析[J].中华流行病学杂志.2003,24(1):50-53.
[5]世界卫生组织专家组织报告.高血压的控制[M].1997,6-15.
[6] EliahouHE. Body Weight reductionnecessary to attainnormtensionintheoverweight hypertensive patient[J]. Inter obesity,1981:5(suppll):157.
[7]张庆珍.高血压发病率与体重指数相关性的调查[J].护理杂志.2001,16(3):184.
[8]魏华,郑建东.北京市朝阳门社区高血压流行情况及相关因素调查[J].疾病监测.2001,16(8):310-312.
[9]刘力生,龚兰生.中国高血压防治指南(试行本)[M].北京:卫生部疾病控制司,1999:11.
[10]潘仰中,蔡运昌,刘君实,等.循证医学心血管病临床应用[M].贵阳:贵州省科技出版社,2000,506-507.
[11] Sacks FM, AppelLJ, MooreTJ, et al. Adietaryapproachtopreventhypertension: areview of the Dietary Approaches to Stop Hypertension(DASH) study[J]. Clin Cardiol,1999,22(7):6-10.
[12]赵连成,周北凡,杨军,等.不同人群的食物摄入量与血压水平的关系[J].中国慢性病预防与控制.1996,4(4):155-159.
[13] KatsuyukiMiura, PhilipGreenland, Jeremiah Stamler, et al. Relation of vegetable,fruit, and meat intaketo7-year blood pressurechange in middle-agedmenthechicagowestern electricstudy[J]. American Journalof Epidemiology,2004,159(6):572-580.
[14] Costa. Factors influencing health of workers and tolerance to shift work[J].Theoretical Issues in Ergonomics Science.2003,4(4):263-288.
[15] Grosswald. Shift work on family satisfaction. Families in Society[J]. The Journalof Contemporary Social Services.2004,85(3):413-423.
[16] Kantermann T, Juda M, Merrow M, et al. The human circadian clock’s seasonaladjustment is disrupted by daylight saving time[J]. Curr Biol.2007,17(22):1996-2000.
[17] Folkard S, Tucker P. Shift work, safety and productivity[J]. Occup Med(Lond).2003,53(2):95-101.
[18] Thompson E. Understanding How Night Work Influences the Everyday FamilyLives of Nurses, Their Husbands and Children[M]. Department of Sociology,University of Surrey: Guildford,2009.
[19]钱令嘉.加强我国职业应激研究[J].中华劳动卫生职业病杂志.2003,21(1):1-2.
[20] Rozanski A, Blumenthal JA, Kaplan J. Impact of psychological factors on thepathogenesis of cardiovascular disease and implications for therapy[J]. Circulation.1999,99(16):2192-2217.
[21] Tsigos C, Chrousos GP. Hypothalamic-pituitary-adrenal axis, neuroendocrinefactors and stress[J]. J Psychosom Res.2002,53(4):865-871.
[22] Jun Shigemi, Yoshio Mino, Tadahiro Ohtsu, et al. Effects of perceived job stresson mental health-A longitudinal survey in a Japanese electronics company[J]. Eur JEpidemiol.2000,16(4):371-376.
[23] Eliassonk, Hjemdahlp, Kahant. Cirulatory and Sympahoadrenal responses tostress in borderline and Estadlished hypertension[J]. J Hypertens.1983,1(2):131-139.
[24] Reinhart GA, Lohmeier TE, Hord CE Jr. Hypertension induced by chronic renaladrenergic stimulation is angiotensin dependent[J]. Hypertension.1995,25(5):940-949.
[25] Kouvonen A, Kivim ki M, Elovainio M, et al. Low organisational justice andheavy drinking: a prospective cohort study [J]. Occup Environ Med.2008,65(1):44-50.
[26] Takaki J, Minoura A, Irimajiri H, et al. Interactive effects of job stress and bodymass index on over-eating [J]. J Occup Health.2010,52(1):66-73.
[27]杨艳,余善法,周世义.职业紧张对吸烟饮酒行为影响[J].中国职业医学.2011,38(6):497-499.
[28] Karasek RA, Theorell TG, Schwartz J, et al. Job, psychological factors andcoronary heart disease. Swedish prospective findings and US prevalence findingsusing a new occupational inference method[J]. Adv Cardiol.1982,29:62-67.
[29] Theorell T, Karasek RA. Current issues relating to psychosocial job strain andcardiovascular disease research[J]. J Occup Health Psychol.1996,1(1):9-26.
[30] Peter R, Alfredsson L, Hammar N, et al. High effort, low reward, andcardiovascular risk factors in employed Swedish men and women: baseline resultsfrom the WOLF Study[J]. J Epidemiol Community Health.1998,52(9):540-547.
[31] Peter R, Siegrist J, Hallqvist J, et al. Psychosocial work environment andmyocardial infarction: improving risk estimation by combining two complementaryjob stress models in the SHEEP Study[J]. J Epidemiol Community Health.2002,56(4):294-300.
[32]余善法,李奎荣,杨艳,等.职业紧张与心血管疾病危险因素的关系[J].中华劳动卫生职业病杂志.2003,21(1):12-15.
[33]姚三巧,范雪云,金玉兰,等.职业紧张对职业人群心血管功能的影响[J].中华劳动卫生职业病杂志.2003,21(1):20-22.
[34]刘宝英,张文昌,杨华,等.职业紧张与高血压发病及其与血压值关系的研究[J].中华劳动卫生职业病杂志.2002,20(5):376-380.
[35]任南,刘宝英,张文昌,等.职业紧张因素与高血压发病关系的配对病例对照研究[J].高血压杂志.2001,9(4):345-347.
[36]黄慧玲,刘宝英,任南,等.职业紧张与高血压发病关系的1:2配比病例对照研究[J].中国公共卫生.2002,18(1):11-13.
[37]曲银娥,赵伯阳,范雪云,等.职业紧张与高血压关系探讨[J].工业卫生与职业病.2002,28(4):197-200.
[38]刘宝英,杨华,任南,等.职业紧张在高血压发病中的作用[J].工业卫生与职业病.2005,31(1):22-25.
[39]周权,刘宝英.工作中社会心理行为因素及与原发性高血压关系的研究[J].海峡预防医学杂志.2008,14(2):20-22.
[40]余善法,周文慧,谷桂珍,等.职业紧张和β2-AR基因多态性与高血压关系的病例对照研究[J].工业卫生与职业病.2010,36(2):93-98.
[41] McCubbin JA, Pilcher JJ, Moore DD. Blood pressure increases during asimulated night shift in persons at risk for hypertension[J]. Int J Behav Med.2010,17(4):314-320.
[42] Sfreddo C, Fuchs SC, Merlo AR, Fuchs FD. Shift work is not associated withhigh blood pressure or prevalence of hypertension[J]. PLoS One.2010,5(12):e15250.
[43] Wang XS, Armstrong ME, Cairns BJ, et al. Shift work and chronic disease: theepidemiological evidence[J]. Occup Med (Lond).2011,61(2):78-89.
[44] Niu W, Qi Y, Hou S, et al. Haplotype-based association of the rennin angiotensinaldosterone system genes polymorphisms with essential hypertension among HanChinese: the Fangshan study[J]. J Hypertens.2009,27(7):1384-1391.
[45] Vangjeli C, Clarke N, Quinn U, et al. Confirmation that the renin gene distalenhancer polymorphism REN-5312C/T is associated with increased blood pressure[J].Circ Cardiovasc Genet.2010,3(1):53-59.
[46] Reba M, Kharrat N, Ayadi I, et al. Haplotype structure of five SNPs within theACE gene in the Tunisian population[J]. Ann Hum Biol.2006,33(3):319-329.
[47] Fuentes RM, Notkola IL, Shemeikka S, et al. Familial aggregation of bloodpressure: a population-based family study in eastern Finland[J]. J Hum Hypertens.2000,14(7):441-445.
[48]叶佳颖,钟久昌,高平进,等.肾素血管紧张素系统基因多态性与高血压[J].心血管康复医学杂志.2008,17(6):587-589.
[49] Dickson ME, Sigmund CD. Genetic basis of hypertension: revisitingangiotensinogen[J]. Hypertension.2006,48(1):14-20.
[50] Allen AM. Role of angiotensin in the rostral ventrolateral medulla in thedevelopment and maintenance of hypertension[J]. Curr Opin Pharmacol.2011,11(2):117-123.
[51] Daugherty A, Poduri A, Chen X, et al. Genetic variants of the Renin Angiotensinsystem: effects on atherosclerosis in experimental models and humans[J]. CurrAtheroscler Rep.2010,12(3):167-173.
[52] Jeunemaitre X, Soubrier F, Kotelevtsev YV, et al. Molecular basis of humanhypertension: role of angiotensinogen[J]. Cell.1992,71(1):169-180.
[53] Brand E, Chatelain N, Paillard F, et al. Detection of putative functionalangiotensinogen (AGT) gene variants controlling plasma AGT levels by combinedsegregation-linkage analysis[J]. Eur J Hum Genet.2002,10(11):715-723.
[54] Knox SS, Guo X, Zhang Y, et al. AGT M235T genotype/anxiety interaction andgender in the HyperGEN study[J]. PLoS One.2010,5(10): e13353.
[55] Goldbergova M, Spinarova L, Spinar J, et al. Association of two angiotensinogengene polymorphisms, M235T and G(-6)A, with chronic heart failure[J]. Int J Cardiol.2003,89(2-3):267-272.
[56] F.A. Sayed-Tabatabaei, B.A. Oostra, A. Isaacs, et al. ACE Polymorphisms[J].Circ.Res.2006,98(9):1123-1133.
[57] Rigat B, Hubert C, Alhenc-Gelas F, et al. An insertion/deletion polymorphism inthe angiotensin I-converting enzyme gene accounting for half the variance of serumenzyme levels[J]. J Clin Invest.1990,86(4):1343-1346.
[58] Hilbert P, Lindpaintner K, Beckmann JS, et al. Chromosomal mapping of twogenetic loci associated with blood-pressure regulation in hereditary hypertensiverats[J]. Nature.1991,353(6344):521-529.
[59] Bonnardeaux A, Davies E, Jeunemaitre X, et al. Angiotensin II type1receptorgene polymorphisms in human essential hypertension[J]. Hypertension.1994,24(1):63-69.
[60] Szpirer C, Rivière M, Szpirer J, et al. Chromosomal assignment of human and rathypertension candidate genes: type1angiotensin II receptor genes and the SA gene[J].J Hypertens.1993,11(9):919-925.
[61] Szolnoki Z, Maasz A, Magyari L, et al. The combination of homozygousMTHFR677T and angiotensin II type-1receptor1166C variants confers the risk ofsmall-vessel-associated ischemic stroke[J]. J Mol Neurosci.2007,31(3):201-207.
[62] Brand E, Chatelain N, Mulatero P, et al. Structural analysis and evaluation of thealdosterone synthase gene in hypertension[J]. Hypertension.1998,32(2):198-204．
[63] Johnson AD, GongY, Wang D et al. Promoter polymorphisms in ACE(angiotensin I-converting enzyme) associated with clinical outcomes inhypertension[J]. Clin Pharmacol Ther.2009,85(1):36-44.
[64] Moore N, Dicker P, O'Brien JK, et al. Renin gene polymorphisms and haplotypes,blood pressure, and responses to renin-angiotensin system inhibition[J]. Hypertension.2007,50(2):340-347.
[65] Gormley K, Bevan S, Markus HS. Polymorphisms in genes of therenin-angiotensin system and cerebral small vessel disease[J]. Cerebrovasc Dis.2007,23(2-3):148-155.
[66]曾光.现代流行病学方法与应用[M].北京医科大学中国协和医科大学联合出版社:176-186.
[67]王培桦,沈洪兵,陈峰,等.叉生分析在基因-环境交互作用研究中的应用与意义[J].中华流行病学杂志.2005,26(1):54-57.
[68]夏果,廖芳芳,邹延峰,等.基因与环境交互作用分析方法在复杂疾病研究中的应用[J].中国卫生统计.2009,26(1):87-90.
[69]张军,于石成,杨功焕,等.遗传易感性-环境交互作用研究方法进展[J].预防医学论坛.2010,16(1):58-62.
[70]柏建岭,荀鹏程,赵杨,等.不完全病例对照研究基因环境交互作用的估计[J].中华流行病学杂志.2006,27(1):72-75.
[71]骆常好,刘桂芬,张爱莲.多因子降维法和Logistic回归交互效应分析对比研究[J].中国药物与临床.2008,8(10):777-779.
[72]赵自强,郑明.应用分类树模型筛选logistic回归中的交互因素[J].中国卫生统计.2007,24(2):114-116.
[73] Ritchie MD, Hahn Lw, Rodi N, et al. Multifactor dimensionality reductionreveals high-order interactions among estrogen-metabolism genes in sporadic breastcancer[J]. Am J Hum Genet.2001,69(1):138-147.
[74]唐迅,李娜,胡永华.应用多因子降维法分析基因基因交互作用[J].中华流行病学杂志.2006,27(5):437-441．
[75] Williams SM, Ritchie MD, Phillips JA, et a1. Multilocus analysis of hypertension:a hierarchical approach[J]. Hum Hered.2004,57(1):28-38．
[76] Brennan P. Gene-environment interaction and aetiology of cancer: what does itmean and how can we measure it[J]? Carcinogenesis.2002,23(3):381-387.
[77]王忠旭,秦汝莉,李玉珍,等.我国23家煤矿企业职业病危害因素及其防护现状[J].环境与职业医学.2009,26(6):565-568.
[78]王雪涛,马骏,关砚生,等.我国地方煤矿职业危害现状调查报告[J].中国安全生产科学技术.2008,4(1):91-94.
[79]范雪云,李庆友,白玉萍,等.煤矿工人职业性多发病研究[J].中华预防医学杂志.1996,30(5):319.
[80]秦天榜.煤矿井下工人高血压患病情况标化分析[J].职业卫生与病伤.1997,12(4):206-207.
[81]梅仁彪,孙桂明,徐展,等.井下作业对高血压矿工血浆皮质醇水平的影响[J].中国行为医学科学.2000,9(1):31-33.
[82]梅仁彪,孙桂明.煤矿井下作业与井下矿工高血压病相关性研究[J].中国工业医学杂志.2001,13(5):299-301.
[83]梅仁彪,孙桂明,徐广绪.煤矿井下作业对高血压矿工血浆血管紧张素II水平的影响[J].中国工业医学杂志.2001,14(5):288-289.
[84]张玉玲,马兰,马铭良.煤矿接尘职工高血压患病情况调查[J].工业卫生与职业病.2001,27(5):285-286.
[85]梅仁彪.高血压矿工血浆肾素、血管紧张素II、醛固酮和皮质醇水平的分析[J].中国工业医学杂志[J].2004,17(4):220-223.
[86]郑国华,李玉,李红,等.煤矿职工原发性高血压及其影响因素分析[J].中国公共卫生.2004,20(6):744-745.
[87]石长胜.煤矿工人高血压危险因素流行病学调查[J].中国职业医学.2007,34(5):439-450.
[88]曹宏,索霞,黄建军.煤矿职工高血压发病危险因素调查[J].职业与健康.2009,25(4):344-346.
[89]王彩云,赵辉.2009年某煤矿40岁以上职工体检结果分析[J].预防医学.2010,48(24):69-70.
[90]王学东,张廷久,等.阜新矿区男性矿工高血压及其危险因素分析[J].中国临床研究.2010,23(5):437-438.
[91]张卫清,信雅菊.煤矿工人高血压状况调查分析[J].中国疗养医学.2011,20(12):1127-1128.
[92]世界卫生组织专家组织报告.高血压的控制[M].北京:人民卫生出版社.1997,6-15.
[93] EliahouHE. Body Weight reductionneces sary to attainnormtensionintheoverweight hypertensive patient[J]. Inter obesity,1981:5(suppll):157.
[94]张庆珍.高血压发病率与体重指数相关性的调查[J].护理杂志.2001,16(3):184.
[95]魏华,郑建东.北京市朝阳门社区高血压流行情况及相关因素调查[J].疾病监测.2001,16(8):310-312.
[96] Pi-Sunyer FX. The epidemiology of central fat distribution in relation todisease[J]. Nutr Rev.2004,62(7Pt2): S120-126.
[97]罗雷,栾荣生,袁萍.中国居民高血压主要危险因素的Meta分析[J].中华流行病学杂志.2003,24(1):50-53.
[98]刘红艳,彭辉,刘奥博,等.中国人原发性高血压危险因素Meat分析[J].中国心血管杂志.2009,14(3):205-209.
[99] KatsuyukiMiura, PhilipGreenland, Jeremiah Stamler, et al. Relation of vegetable,fruit, and meat intaketo7-year blood pressurechange in middle-agedmenthechicagowestern electricstudy[J]. American Journalof Epidemiology,2004,159(6):572-580.
[100]赵文华,王军波,肖颖,等.膳食及营养因素对农村居民高血压患病影响的多因素分析[J].营养学报.2002,24(3):274-277.
[101] Wildman RP, Gu D, Muntner P, et al. Alcohol intakeandhyperten-sion subtypesin Chinese men[J]. Journalof Hypertension.2005,23(4):737-743.
[102]李军昕,张波.不同年代中国人群高血压病危险因素的Meta分析[J].中国循证医学杂志.2009,9(12):1302-1309.
[103] Rhee MY, Na SH, Kim YK, et al. Acute effects of cigarette smoking on arterialstiffness and blood pressure in male smokers with hypertension[J]. Am J Hypertens.2007,20(6):637-641.
[104]杨波,邱泉,栾玉明,等.海珠区4062名男性常住居民吸烟指数对高血压影响分析[J].现代预防医学.2010,37(8):1553-1555.
[105] Partinen M, Palom ki H. Snoring and cerebral infarction[J]. Lancet.1985,2(8468):1325-1326.
[106]徐宝珠.打鼾与脑血管疾病关系的调查[J].中国慢性病预防与控制.1999,7(l):22.
[107]马金香,孙业桓,曹多志,等.男性打鼾与高血压的关系[J].中国慢性病预防与控制.2005,13(2):60-63.
[108] Chearskul S, Charoenlarp K, Thongtang V, et al. Study of plasma hormones andlipids in healthy elderly Thais compared to patients with chronic diseases: diabetesmellitus, essential hypertension and coronary heart disease[J]. J Med Assoc Thai.2000,83(3):266-277.
[109] Ridker PM. High-sensitivity C-reactive protein: potential adjunct for global riskassessment in the primary prevention of cardiovascular disease[J]. Circulation.2001,103(13):1813-1818.
[110]李莹,陈志红,周北凡,等.我国中年人群血清TC/HDLC比值与缺血性和出血性脑卒中发病危险性[J].中华神经科杂志.2005,38(5):305-308.
[111] Sfreddo C, Fuchs SC, Merlo AR, Fuchs FD. Shift work is not associated withhigh blood pressure or prevalence of hypertension[J]. PLoS One.2010,5(12):e15250.
[112] McCubbin JA, Pilcher JJ, Moore DD. Blood pressure increases during asimulated night shift in persons at risk for hypertension[J]. Int J Behav Med.2010,17(4):314-320.
[113]石长胜.煤矿工人高血压危险因素流行病学调查[J].中国职业医学.2007,34(5):439-440.
[114]阎进德,姚三巧,白玉萍,等.职业紧张对长途客车司机血压的影响[J].工业卫生与职业病.2000,26(3):134-136.
[115]刘静波,张幼辰,俞顺章.血管紧张素原基因多态性与原发性高血压关系的研究[J].中华流行病学杂志.2000,21(6):407-409.
[116] Nishiuma S, Kario K, Kayaba K, et al. Effect of the angiotensinogen geneMet235-The variant on blood pressure and other cardiovascular risk factors in twoJapanses populations[J]. J Hypertens.1995,13(7):717-722.
[117] Knox SS, Guo X, Zhang Y, et al. AGT M235T genotype/anxiety interaction andgender in the HyperGEN study[J]. PLoS One.2010,5(10): e13353.
[118] Goldbergova M, Spinarova L, Spinar J, et al. Association of twoangiotensinogen gene polymorphisms, M235T and G(-6)A, with chronic heartfailure[J]. Int J Cardiol.2003,89(2-3):267-72.
[119] Ortlepp JR, Metrikat J, Mevissen V, et al. Relation between the angiotensinogen(AGT) M235T gene polymorphism and blood pressure in a large, homogeneous studypopulation[J]. J Hum Hypertens.2003,17(8):555-559.
[120] Mondry A, Loh M, Liu P, et al. Polymorphisms of the insertion/deletion ACEand M235T AGT genes and hypertension: surprising new findings and meta-analysisof data. BMC Nephrol.2005,11(6):1-2.
[121] F.A. Sayed-Tabatabaei, B.A. Oostra, A. Isaacs, et al. ACE Polymorphisms[J].Circ.Res.2006,98(9):1123-1133.
[122] Rigat B, Hubert C, Alhenc-Gelas F, et al. An insertion/deletion polymorphism inthe angiotensin I-converting enzyme gene accounting for half the variance of serumenzyme levels[J]. J Clin Invest.1990,86(4):1343-1346.
[123] Hilbert P, Lindpaintner K, Beckmann JS, et al. Chromosomal mapping of twogenetic loci associated with blood-pressure regulation in hereditary hypertensiverats[J]. Nature.1991,353(6344):521-529.
[124] Gunes HV, Ata N, Degirmenci I, et al. Frequency of angiotensin-convertingenzyme gene polymorphism in Turkish hypertensive patients[J]. Int J Clin Pract.2004,58(9):838-843.
[125] Stefansson B, Ricksten A, Rymo L, et al. Angiotensin-converting enzyme geneI/D polymorphism in malignant hypertension[J]. Blood Press.2000,9(2-3):104-109.
[126] Rigat B，Hubert C，Corvol P，et a1．PCR detection of the insertion／deletionpolymorphism of the human angiotensin converting enzyme gene(DCPl)[J]．NucleicAcids Res.1992,20(6):1433．
[127]李娜，郭淑霞，张翼华，等.哈萨克族高血压与血管紧张素转换酶基因多态性[J].中国公共卫生,2008,24(3):274-275.
[128] Ned RM, Yesupriya A, Imperatore G, et al. The ACE I/D Polymorphism in USAdults: Limited Evidence of Association With Hypertension-Related Traits andSex-Specific Effects by Race/Ethnicity[J]. Am J Hypertens.2011,13. doi:10.1038/ajh.2011.182.
[129] Yanyan L. The angiotensin converting enzyme gene insertion/deletion (I/D)polymorphism and essential hypertension in the Chinese population: a meta-analysisincluding21058participants[J]. Intern Med J.2011,1. doi:10.1111/j.1445-5994.2011.02584.x.
[130]张琦,沈志霞,李宏芬,等.血管紧张素转换酶基因插入/缺失多态性在人群中的分布及其与原发性高血压的关系[J].中华医学遗传学杂志.2003,20(5):438-440.
[131]李宏芬,沈志霞,常延河,等.中国人群血管紧张素转换酶基因与血管紧张素Ⅱ21型受体基因A1166C单核苷酸多态性分析[J].中华检验医学杂志,2003,26(2):89-92.
[132]刘丽娟,佟伟军,张永红,等.蒙古族ACE基因多态性与高血压关系的研究[J].中国公共卫生.2003,19(4):392-393.
[133] Szpirer C, Rivière M, Szpirer J, et al. Chromosomal assignment of human andrat hypertension candidate genes: type1angiotensin II receptor genes and the SAgene[J]. J Hypertens.1993,11(9):919-925.
[134] Kobashi G, Hata A, Ohta K, et al. A1166C variant of angiotensin II type1receptor gene is associated with severe hypertension in pregnancy independently ofT235variant of angiotensinogen gene[J]. J Hum Genet.2004,49(4):182-186.
[135] Sugimoto K, Katsuya T, Ohkubo T, et al. Association between angiotensin IItype1receptor genepolymorphismandessential hypertension: the Ohasama Study[J].Hypertens Res.2004,27(8):551-556.
[136]徐欣,杨承健,郑义通,等.血管紧张素II-1型受体基因A1166C多态性与高血压的相关研究初探[J].中国微循环.2009,13(1):49-52.
[137]左彦方,龙爱梅.血管紧张素II1型受体基因A1166C多态性与原发性高血压易感性的Meat分析[J].循证医学.2008,8(6):349-352.
[138] Niu W, Qi Y. Association of the angiotensin II type I receptor gene+1166A>Cpolymorphism with hypertension risk: evidence from a meta-analysis of16474subjects[J]. Hypertens Res.2010,33(11):1137-1143.
[139] Palatini P, Ceolotto G, Dorigatti F, et al. Angiotensin II type1receptor genepolymorphism predicts development of hypertension and metabolic syndrome[J]. AmJ Hypertens.2009,22(2):208-214.
[140] Brand E, Chatelain N, Mulatero P, et al. Structural analysis and evaluation ofthe aldosterone synthase gene in hypertension[J]. Hypertension,1998,32:198-204．
[141] Sookoian S, Gianotti TF, González CD, et al. Association of the C-344Taldosterone synthase gene variant with essential hypertension: a meta-analysis[J]. JHypertens.2007,25(1):5-13.
[142] Hlubocká Z, Jáchymová M, Heller S, et al. Association of the-344T/Caldosterone synthase gene variant with essential hypertension[J]. Physiol Res.2009,58(6):785-792.
[143] Sun X, Yang J, Hou X, et al. Relationship between-344T/C polymorphism inthe aldosterone synthase gene and atrial fibrillation in patients with essentialhypertension[J]. J Renin Angiotensin Aldosterone Syst.2011,12(4):557-563.
[144] NIU WQ, WANG JB, LI SJ, et al. Relationship between Aldosterone Synthasegene (CYP11B2) Polymorphisms and Essential Hypertension in a Northern ChineseHan Population[J]. Acta Acad Med Sin.2007,29(3):329-335.
[145]徐新娟,汪师贞,林仁勇,等.新疆哈萨克族隔离群醛固酮合成酶基因多态性与原发性高血压的关联性[J].中华医学遗传学杂志.2004,21(6):622-624.
[146]李庆祥,张宇清,靳凤艳,等.醛固酮合成酶(CYP11B2)基因T(-344)C多态性与高血压病相关性研究[J].高血压杂志.2003,11(3):238-240.
[147] Tsujita Y, Iwai N, Katsuya T, et al. Lack of association between geneticpolymorphism of CYP11B2and hypertension in Japanese: the Suita Study[J].Hypertens Res.2001,24(2):105-109.
[148] Alvarez-Madrazo S, Connell JM, Freel EM. Role of genetic variation inregulation of aldosterone biosynthesis[J]. Endocr Dev.2011,20:106-115.
[149] Cheng X, Xu G. A systemic review of the relationship between aldosteronesynthase-344C/T polymorphism and hypertension in Han[J]. Clin Exp Hypertens.2010,32(5):301-307.
1Costa. Factors influencing health of workers and tolerance to shift work. TheoreticalIssues in Ergonomics Science.2003,4(4),263-288.
2Grosswald. Shift work on family satisfaction. Families in Society: The Journal ofContemporary Social Services.2004,85(3),413-423.
3Anders Knutsson. Methodological Aspects of Shift-Work Research. ChronobiologyInternational.2004,21(6):889-897.
4Akerstedt T. Shift work and disturbed sleep/wakefulness. Occup Med(Lond).2003,53(2):89-94.
5Roenneberg T, Kuehnle T, Juda M, et al. Epidemiology of the human circadianclock. Sleep Med. Rev.2007,11(6):429-438.
6Kantermann T, Juda M, Merrow M, et al. The human circadian clock’s seasonaladjustment is dis-rupted by daylight saving time. Curr Biol.2007,17(22):1996-2000.
7Baker D. The use and health consequences of shift work. Int J Health Serv.1980,10(3):405-420.
8Folkard S, Tucker P. Shift work, safety and productivity. Occup Med(Lond).2003,53(2):5-101.
9Foster RG, Wulff K. The rhythm of rest and excess. Nat Rev Neurosci.2005,6(5):407-414.
10Haus E, Smolensky M. Biological clocks and shift work: circadian dysregulationand potential long-term effects. Cancer Causes Control.2006,17(4):489-500.
11Knutsson A. Health disorders of shift workers. Occup Med(Lond).2003,53(2):103-108.
12Whitehead DC, Thomas H, Jr, Slapper DR. A rational approach to shift work inemergency medicine. Ann Emerg Med.1992,21(10):1250-1258.
13Thompson E.Understanding How Night Work Influences the Everyday FamilyLives of Nurses, Their Husbands and Children. Department of Sociology, Universityof Surrey: Guildford,2009.
14Santhi N, Aeschbach D, Horowitz TS, et al. The impact of sleep timing and brightlight xposure on attentional impairment during night work. J Biol Rhythms,2008,23(4):341-52.
15Sudo N, Ohtsuka R. Fatigue complaints among female shift workers in a computerfactory of Japan. J Hum Ergol (Tokyo).2002,31(1-2):41-51.
16Akerstedt T, Knutsson A, Westerholm P, et al. Mental fatigue, work and sleep. JPsychosom Res.2004,57(5):427-433.
17Jianhua SHEN, Leigh C.P. Botly, Sharon A.Chung, et al. Fatigue and shift work.J.Sleep RES.2006(15):1-5.
18Hossain J L, Reinish L W, Kayumov, et al. Underlying sleep pathology may causechronic high fatigue in shift-workers. Sleep Res.2003(12):223-230.
19Zhen Lu W, Ann Gwee K, Yu Ho K. Functional bowel disorders in rotating shiftnurses may be related to sleep disturbances. Eur J Gastroenterol Hepatol.2006,18(6):623-627.
20Geiger Brown J, Rogers VE, Trinkoff AM, et al. Sleep, sleepiness, fatigue, andperformance of12-hour-shift nurses. Chronobiol Int.2012,29(2):211-219.
21Parshuram CS, To T, Seto W, et al. Systematic evaluation of errors occurringduring the preparation of intravenous medication. Can Med Assoc J.2008,178(1):42–48.
22Fisman DN, Harris AD, Rubin M, et al. Fatigue increases the risk of injury fromsharp devices in medical trainees: Results from a case-crossover study. Infect ControlHosp Epidemiol.2007,28(1):10-17.
23Baker K, Olson J, Morisseau D. Work practices, fatigue, and nuclear power plantsafety performance. Hum Factors.1994,36(2):244-257.
24Mulgrew AT, Ryan CF, Fleetham JA, et al. The impact of obstructive sleep apneaand daytime sleepiness on work limitation. Sleep Med.2007,9(1):42-53.
25Moller HJ, Kayumov L, Bulmash EL, et al. Simulator performance, microsleepepisodes, and subjec-tive sleepiness: Normative data using convergentmethod-ologies to assess driver drowsiness. J Psychosom Res.2006,61(3):335-342.
26De Pinho RS, da Silva-Junior FP, Bastos JP, et al. Hypersomnolence and accidentsin truck drivers: A cross-sectional study. Chronobiol Int.2006(23):963-971.
27Van Amelsvoort LG, Jansen NW, Swaen GM, et al. Direction of shift rotationamong three-shift workers in relation to psychological health and work-familyconflict. Scand J Work Environ Health.2004,30(2):149-156.
28Hossain NK, Irvine J, Ritvo P, et al. Evaluation and treatment of sleep complaints:Patients’subjective responses. Psychother Psychosom.2007,76(6):395-399.
29Shapiro CM, Auch C, Reimer M, et al. A new approach to the construct ofalertness. J Psychosom Res.2006,60(6):595-603.
30B ggild H, Knutsson A. Shift work, risk factors and cardiovascular disease. ScandJ Work Environ Health.1999,25(2):85-99.
31Frost P, Kolstad HA, Bonde JP. Shift work and the risk of ischemic heart disease-asystematic review of the epidemiologic evidence. Scand J Work Environ Health.2009,35(3):163-79.
32Puttonen S, Kivim ki M, Elovainio M, et al. Shift work in young adults andcarotid artery intima-media thickness: The Cardiovascular Risk in Young Finns study.Atherosclerosis.2009,205(2):608-613.
33Fujino Y, Iso H, Tamakoshi A, et al. A prospective cohort study of shift work andrisk of ischemic heart disease in Japanese male workers. Am J Epidemiol.2006,164(2):128-135.
34Yadegarfar G, McNamee R. Shift work, confounding and death from ischaemicheart disease. Occup Environ Med.2008,65(3):158-163.
35Radi S, Ostry A, Lamontagne AD. Job stress and other working conditions:relationships with smoking behaviors in a representative sample of workingAustralians. Am J Ind Med.2007,50(8):584-596.
36Van Amelsvoort LG, Jansen NW, Kant I. Smoking among shift workers: more thana confounding factor. Chronobiol Int.2006,23(6):1105-1113.
37Nabe-Nielsen K, Garde AH, Tüchsen F, et al. Cardiovascular risk factors andprimary selection into shift work. Scand J Work Environ Health.2008,34(3):206-212.
38Lennern s M, Hambraeus L, kerstedt T. Shift related dietary intake in day andshift workers. Appetite.1995,25(3):253-265.
39Morikawa Y, Miura K, Sasaki S, et al. Evaluation of the effects of shift work onnutrient intake: a cross-sectional study. J Occup Health.2008,50(3):270-78.
40Biggi N, Consonni D, Galluzzo V, et al. Metabolic syndrome in permanent nightworkers. Chronobiol Int.2008,25(2):443-454.
41Dochi M, Suwazono Y, Sakata K, et al. Shift work is a risk factor for increasedtotal cholesterol level: a14-year prospective cohort study in6886male workers.Occup Environ Med.2009,66(9):592-597.
42Morikawa Y, Nakagawa H, Miura K, et al. Effect of shift work on body mass indexand metabolic parameters. Scand J Work Environ Health.2007,33(1):45-50.
43Ghiasvand M, Heshmat R, Golpira R, et al. Shift working and risk of lipiddisorders: a cross-sectional study. Lipids Health Dis.2006,10(4):5-9.
44Sookoian S, Gemma C, Fernandez Gianotti T, et al. Effects of rotating shift workon biomarkers of metabolic syndrome and inflammation. J Intern Med.2007,261(3):285-292.
45Cappuccio FP, Taggart FM, Kandala NB, et al. Meta-analysis of short sleepduration and obesity in children and adults. Sleep.2008,31(5):619-626.
46Marshall NS, Glozier N, Grunstein RR. Is sleep duration related to obesity? acritical review of the epidemiological evidence. Sleep Med Rev.2008,12(4):289-298.
47Suwazono Y, Dochi M, Sakata K, et al. A longitudinal study on the effect of shiftwork on weight gain in male Japanese workers. Obesity (Silver Spring).2008,16(8):1887-1893.
48Karasek RA, Theorell T. Healthy work: stress, productivity, and the reconstructionof working life. New York (NY): Basic Books,1990.
49Ala-Mursula L, Vahtera J, Pentti J, et al. Effect of employee worktime control onhealth: a prospective cohort study. Occup Environ Med.2004,61(3):254-261.
50Ala-Mursula L, Vahtera J, Kivim ki M, et al. Employee control over workingtimes: associations with subjective health and sickness absences. J EpidemiolCommunity Health.2002,56(4):272-278.
51Siegrist J, Peter R, Junge A, et al. Low status control, high effort at work andischemic heart disease: prospective evidence from blue-collar men. Soc Sci Med.1990,31(10):1127-1134.
52Peter R, Alfredsson L, Knutsson A, et al. Does a stressful psychosocial workenvironment mediate the effects of shift work on cardiovascular risk factors? Scand JWork Environ Health.1999,25(4):376-81.
53Albertsen K, Rafnsdóttir G, Grimsmo A, et al. Workhours and worklife balance.SJWEH Suppl.2008,(5):14-21.
54Costa G, Sartori S, kerstedt T. Influence of flexibility and variability of workinghours on health and well-being. Chronobiol Int.2006,23(6):1125-1137.
55Alberti KG, Eckel RH, Grundy SM, et al. Harmonizing the metabolic syndrome: ajoint interim statement of the In-ternational Diabetes Federation Task Force onEpidemiology and Prevention; National Heart, Lung, and Blood Institute; AmericanHeart Association; World Heart Feder-ation; International Atherosclerosis Society;and Interna-tional Association for the Study of Obesity. Circulation.2009,120(16):1640-1645.
56Galassi A, Reynolds K, He J. Metabolic syndrome and risk of cardiovasculardisease: a meta-analysis. Am J Med.2006,119(10):812-819.
57Karlsson B, Knutsson A, Lindahl B. Is there an association between shift work andhaving a metabolic syndrome? Results from a population based study of27,485people. Occup Environ Med.2001,58(11):747-752.
58Lin YC, Hsiao TJ, Chen PC. Persistent rotating shift-work exposure acceleratesdevelopment of metabolic syndrome among middle-aged female employees: afive-year follow-up. Chronobiol Int2009,26(4):740-755.
59Lin YC, Hsiao TJ, Chen PC. Shift work aggravates metabolic syndromedevelopment among early-middle-aged males with elevated ALT. Wor ld JGastroenterol.2009,15(45):5654-5661.
60De Bacquer D, Van Risseghem M, Clays E, et al. Rotating shift work and themet-abolic syndrome: a prospective study. Int J Epidemiol.2009,38(3):848-854.
61Sookoian S, Gemma C, Gianotti TF, et al. Effects of rotating shift work onbiomarkers of metabolic syndrome and inflammation. J Int Med.2007,261(3):285-292.
62Pietroiusti A, Neri A, Somma G, et al. Incidence of metabolic syndrome amongnight shift health care workers. Occup Environ Med.2010,67(1):54-57.
63Esquirol Y, Bongard V, Mabile L, et al. Shift work and metabolic syndrome:respective impacts of job strain, physical activity, and dietary rhythms. Chronobiol IntJ Biol Med Rhythm Res.2009,26(3):544-559.
64Mikuni E, Ohoshi T, Hayashi K, et al. Glucose intolerance in an employedpopulation. Tohoku J Exp Med.1983,141(Suppl):251-256.
65Kawakami N, Araki S, Takatsuka N, et al. Overtime, psychosocial workingconditions, and occurrence of non-insulin dependent diabetes mellitus in Japanesemen. J Epidemiol Commun Health.1999,53(6):359-363.
66Nagaya T, Yoshida H, Takahashi H, et al. Markers of insulin resistance in day andshift workers aged30-59years. Int Arch Occup Environ Health.2002,75(8):562-568.
67Morikawa Y, Nakagawa H, Miura K, et al. Shift work and the risk of diabetesmellitus among Japanese male factory work-ers. Scand J Work Environ Health.2005,31(3):179-183.
68Karlsson B, Alfredsson L, Knutsson A, et al. Total mortality and cause-specificmortality of Swedish shift-and dayworkers in the pulp and paper indus-try in1952-2001. Scand J Work Environ Health2005,31(1):30-35.
69Kroenke CH, Spiegelman D, Manson J, et al. Work characteristics and incidence oftype2diabetes in women. Am J Epidemiol.2007,165(2):175-183.
70Pan A, Schernhammer ES, Sun Q, et al. Rotating night shift work and risk of type2diabetes: two prospective cohort studies in women. PLoS Med.2011,8(12):e1001141.
71Akerstedt T, Knutsson A, Alfredsson L, et al. Shift work and cardiovascular disease.Scand J Work Environ Health.1984,10(6):409-414.
72Knutsson A, Akerstedt T, Jonsson BG, et al. Increased risk of ischaemic heartdisease in shift workers. Lan-cet.1986,2(8498):89-92.
73Kristensen TS. Cardiovascular diseases and the work environment. A criticalreview of the epidemiologic literature on nonchemical factors. Scand J Work EnvironHealth.1989,15(3):165-179.
74Boggild H, Knutsson A. Shift work, risk factors and cardio-vascular disease. ScandJ Work Environ Health.1999,25(2):85-99.
75Haupt CM, Alte D, Do¨rr M, et al. The relation of exposure to shift work withatherosclerosis and myocardial infarction in a general population. Atherosclerosis.2008,201(1):205-211.
76Ellingsen T, Bener A, Gehani AA. Study of shift work and risk of coronary events.J R Soc Promot Health.2007,127(6):265-267.
77Hermansson J, Gillander Gadin K, Karlsson B, et al. Ischemic stroke and shiftwork. Scand J Work Environ Health.2007,33(6):435-439.
78Brown DL, Feskanich D, Sa′nchez BN, et al. Rotating night shift work and therisk of ischemic stroke. Am J Epidemiol.2009,169(11):1370-1377.
79Puttonen S, Ha¨ rma¨ M, Hublin C. Shiftwork and cardiovascular disease-pathways from circadian stress to morbidity. Scand J Work Environ Health.2010,36(2):96-108.
80Hansson GK. Inflammation, atherosclerosis, and coronary artery disease. N Engl JMed.2005,352(16):1685-1695.
81Okamoto H, Tsunoda T, Teruya K, et al. An occupational health study ofemergency physicians in Japan: health assessment by immune variables(CD4, CD8,CD56, and NK cell activity) at the beginning of work. J Occup Health.2008,50(2):136-146.
82Copertaro A, Bracci M, Barbaresi M, et al. Assessment of cardiovascular risk inshift healthcare workers. Eur J Cardiovasc Prev Rehabil.2008,15(2):224-229.
83Martins PJ, D’Almeida V, Vergani N, et al. Increased plasma homocysteine levelsin shift working bus drivers. Occup Environ Med.2003,60(9):662-666.
84Lavie L, Lavie P. Elevated plasma homocysteine in older shift-workers: a potentialrisk factor for cardiovascular morbidity. Chronobiol Int.2007,24(1):115-128.
85Antoniades C, Antonopoulos AS, Tousoulis D, et al. Homocysteine and coronaryatherosclerosis: from folate fortification to the recent clinical trials. Eur Heart J.2009,30(1):6-15.
86McCully KS. Chemical pathology of homocysteine, IV: excitotoxicity, oxidativestress, endothelial dysfunction, and inflammation. Ann Clin Lab Sci.2009,39(3):219-232.
87Amir O, Alroy S, Schliamser JE, et al. Brachial artery endothelial function inresidents and fellows working night shifts. Am J Cardiol.2004,93(7):947-949.
88Haupt CM, Alte D, Dorr M, et al. The relation of exposure to shift work withatherosclerosis and myocardial infarction in a general population. Atherosclerosis.2008,201(1):205-211.
89Puttonen S, Kivim ki M, Elovainio M, et al. Shift work in young adults andcarotid artery intima-media thickness: The Cardiovascular Risk in Young Finns study.Atherosclerosis.2009,205(2):608-613.
90Chung MH, Kuo TB, Hsu N, et al. Sleep and autonomic nervous system changesenhanced cardiac sympathetic modulations during sleep in permanent night shiftnurses. Scand J Work Environ Health.2009,35(3):180-187.
91Furlan R, Barbic F, Piazza S, et al. Modifications of ardiac autonomic profileassociated with a shift schedule of work. Circulation.2000,102(16):1912-1916.
92Ohira T, Tanigawa T, Iso H, et al. Effects of shift work on24-hour ambulatoryblood pressure and its variability among Japanese workers. Scand J Work EnvironHealth.2000,26(5):421-426.
93Suwazono Y, Dochi M, Sakata K, et al. Shift work is a risk factor for increasedblood pressure in Japanese men: a14-year historical cohort study. Hypertension.2008,52(3):581-586.
94Lo SH, Liau CS, Hwang JS, et al. Dynamic blood pressure changes and recoveryunder different work shifts in young women. Am J Hypertens.2008,21(7):759-764.
95Virkkunen H, H rm M, Kauppinen T, et al. Shift work, occupational noise andhysical workload with ensuing development of blood pressure and their joint effect onthe risk of coronary heart disease. Scand J Work Environ Health.2007,33(6):425-434.
96Sfreddo C, Fuchs SC, Merlo A′R, et al. Shift work is not associated with highblood pressure or prevalence of hypertension. PLoS ONE5(12): e15250.doi:10.1371/journal.pone.0015250.
97Preetha Anand, Ajaikumar B, Kunnumakara, et al. Cancer is a Preventable Diseasethat Requires Major Lifestyle Changes. Pharm Res.2008,25(9):2097-2116.
98Straif K, Baan R, Grosse Y, et al. Carcinogenicity of shift work, painting, andfire-fighting. Lancet Oncol.2007,8(12):1065-1066.
99Megdal SP, Kroenke CH, Laden F, et al. Night work and breast cancer risk: asystematic review and meta-analysis. Eur J Cancer.2005,41(13):2023-2032.
100Kolstad HA. Nightshift work and risk of breast cancer and other cancers: Acritical review of the epidemiologic evidence. Scand J Work Environ Health.2008,34(1):5-22.
101Kubo T, Ozasa K, Mikami K, et al. Prospective cohort study of the risk ofprostate cancer among rotating shift workers: findings from the Japan CollaborativeCohort Study. Am J Epidemiol.2006,164(6):549-555.
102Conlon M, Lightfoot N, Kreiger N. Rotating shift work and risk of prostatecancer. Epidemiology.2007,18(1):182-183.
103Schernhammer ES, Laden F, Speizer FE, et al. Night-shift work and risk ofcolorectal cancer in the Nurses’ Health Study. J Natl Cancer Inst.2003,95(11):825-828.
104Schwartzbaum J, Ahlbom A, Feychting M. Cohort study of cancer risk amongmale and female shift workers. Scand J Work Environ Health.2007,33(5):336-343.
105Tynes T, Hannevik M, Andersen A, et al. Incidence of breast cancer in Norwegianfe-male radio and telegraph operators. Cancer Causes Control.1996,7(2):197-204.
106Lahti TA, Partonen T, Kyyro¨ nen P, et al. Night-time work predisposes tonon-Hodgkin lymphoma. Int J Cancer.2008,123(9):2148-2151.
[1] Tamaki S, Iwai N, Tsujita Y, et al. Genetic polymorphism of CYP11B2gene andhypertension in Japanese[J]. Hypertension.1999,33:266-270.
[2]梅仁彪,孙桂明.煤矿井下作业与井下矿工高血压病相关性研究[J].中国工业医学杂志.2000,13(5):299-301.
[3] Komiya I et al. Lys(173)Arg and344T/C variants of CYP11B2in Japanesepatients with low-renin hyper-tension[J]. Hypertension2000,35:699-703.
[4] Brand E, Chatelain N, Mulatero P, et al. Structural analysis and evaluation of thealdosterone synthase gene in hypertension[J]. Hypertension.1998,32:198-204．
[5] Sookoian S, Gianotti TF, González CD, et al. Association of the C-344Taldosterone synthase gene variant with essential hypertension: a meta-analysis[J]. JHypertens.2007,25(1):5-13.
[6] Hlubocká Z, Jáchymová M, Heller S, Umnerová V, et al. Association of the-344T/C aldosterone synthase gene variant with essential hypertension[J]. Physiol Res.2009,58(6):785-792.
[7] Sun X, Yang J, Hou X, et al. Relationship between-344T/C polymorphism in thealdosterone synthase gene and atrial fibrillation in patients with essentialhypertension[J]. J Renin Angiotensin Aldosterone Syst.2011,12(4):557-563.
[8]李庆祥,张宇清,靳凤艳等.醛固酮合成酶（CYP11B2）基因T(-344)C多态性与高血压病相关性研究[J].高血压杂志.2003,11(3):238-240.
[9] Tsujita Y, Iwai N, Katsuya T, et al. Lack of association between geneticpolymorphism of CYP11B2and hypertension in Japanese: the Suita Study[J].Hypertens Res.2001,24(2):105-109.
[10] NIU Wen-quan, WANG Jiang-bing, LI Su-jie, et al. Relationship betweenAldosterone Synthase gene (CYP11B2) Polymorphisms and Essential Hypertensionin a Northern Chinese Han Population[J]. Acta Acad Med Sin.2007,29(3):329-335.
[11] Kumar NN, Benjafield AV, Lin RCY, et al. Haplotype analysis of aldosteronesynthase gene (CYP11B2) polymorphism shows association with essentialhypertension[J]. J Hypertens.2003,21:1331-1337.
© 2004-2018 中国地质图书馆版权所有 京ICP备05064691号 京公网安备11010802017129号 地址：北京市海淀区学院路29号 邮编：100083 电话：办公室：(+86 10)66554848；文献借阅、咨询服务、科技查新：66554700 |