SLC12A3基因rs11643718位点基因多态性与EH发病的多因素分析
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摘要
为探讨SLC12A3基因rs11643718位点基因多态性与原发性高血压(EH)发病的关系及对EH患者的健康教育对策,本研究选取心血管内科门诊确诊的高血压患者150例(EH组)、健康自愿者300例进行调查(对照组),采用聚合酶链反应(PCR)技术检测两组人群的SLC12A3基因rs11643718位点基因多态性,并收集两组的一般资料、生活行为方式资料,采用多因素分析EH发病的危险因素及其防治对策。研究发现EH组患者的SLC12A3基因rs11643718位点基因型与对照组比较差异无统计学意义(p>0.05);EH组SLC12A3基因rs11643718位点等位基因频率A (10.57%)显著的低于对照组"16.33%",差异具有统计学意义(p<0.05);采用Logistic回归分析可知,食盐量、LDL-C、TC、TG增加、SLC12A3基因rs11643718位点等位基因频率A降低是人群发生高血压的独立危险因素,差异有统计学意义(p<0.05)。本研究的结果说明,高血压的发病受多种因素的影响,SLC12A3基因rs11643718位点等位基因频率A表达可以降低人群发生高血压疾病的风险。
To explore the relationship between SLC12 A3 gene polymorphism at rs11643718 locus and the incidence of primary hypertension(EH) and the health education strategies for EH patients,150 patients with hypertension were selected(EH group) and 300 cases of healthy volunteers(control group) were investigated.Polymerase chain reaction(PCR) was used to detect the gene polymorphisms in SLC12 A3 gene rs11643718 in two groups, and collected the data of the two groups of general information and the way of life. Multivariate analysis was used to evaluate the risk factors of EH and its countermeasures. It was found that there was no significant differencein SLC12 A3 gene rs11643718 polymorphism between control group and the EH group(p>0.05); group EH SLC12 A3 gene rs11643718 allele frequency A(10.57%) was significantly lower than that of the control group(16.33%), and the difference was statistically significant(p<0.05). Logistic regression analysis showed that the amount of salt, LDL-C, TC, TG, and decrease of allele frequency A of SLC12 A3 gene rs11643718 were statistically significant independent risk factors of hypertension(p<0.05). It could be concluded that the incidence of hypertension was affected by many factors, the rs11643718 allele frequency A of SLC12 A3 gene expression could reduce the risk of hypertension in the population.
To explore the relationship between SLC12 A3 gene polymorphism at rs11643718 locus and the incidence of primary hypertension(EH) and the health education strategies for EH patients,150 patients with hypertension were selected(EH group) and 300 cases of healthy volunteers(control group) were investigated.Polymerase chain reaction(PCR) was used to detect the gene polymorphisms in SLC12 A3 gene rs11643718 in two groups, and collected the data of the two groups of general information and the way of life. Multivariate analysis was used to evaluate the risk factors of EH and its countermeasures. It was found that there was no significant differencein SLC12 A3 gene rs11643718 polymorphism between control group and the EH group(p>0.05); group EH SLC12 A3 gene rs11643718 allele frequency A(10.57%) was significantly lower than that of the control group(16.33%), and the difference was statistically significant(p<0.05). Logistic regression analysis showed that the amount of salt, LDL-C, TC, TG, and decrease of allele frequency A of SLC12 A3 gene rs11643718 were statistically significant independent risk factors of hypertension(p<0.05). It could be concluded that the incidence of hypertension was affected by many factors, the rs11643718 allele frequency A of SLC12 A3 gene expression could reduce the risk of hypertension in the population.
引文
Bodhini D.,Chidambaram M.,Liju S.,Revathi B.,Laasya D.,Sathish N.,Kanthimathi S.,Ghosh S.,Anjana R.M.,Mohan V.,and Radha V.,2016,Association of rs11643718SLC12A3 and rs741301 ELMO1 variants with diabetic nephropathy in south indian population,Ann.Hum.Genet.,80(6):336-341
Burt V.L.,Whelton P.,Roccella E.J.,Brown C.,Cutler J.A.,Higgins M.,Horan M.J.,and Labarthe D.,1995,Prevalence of hypertension in the US adult population:results from the third national health and nutrition examination survey,1988-1991,Hypertension,25(3):305-313
Carretero O.A.,and Oparil S.,2000,Essential hypertension.Part I:definition and etiology,Circulation,101(3):329-335
Chen F.,Zhang Y.,Wang H.,Youyang J.Y.,Munila·Ainiwaer,Kalibinuer·Yakefu,and Yang M.Z.,2015,Association of plasma homocysteine level and polymorphism of methione synthase reductase gene with essential hypertension in ethnic Uyghurs and Hans from Xinjiang,Zhonghua Yixue Yichuangxue Zazhi(Chinese Journal of Medical Genetics),32(4):548-553(陈芳,张颖,王红,欧阳菊艳,木尼拉·艾尼瓦尔,卡丽比努尔·雅合甫,杨梦智,2015,同型半胱氨酸水平及其MSR基因多态性与新疆维吾尔族、汉族原发性高血压的相关性,中华医学遗传学杂志,32(4):548-553)
Chen Y.,Gong Y.W.,Zhou X.Q.,Xu H.X.,Yang L.,and Wu Y.Y.,2016,Association between single nucleotide polymorphism of adenylyl cyclase 3 and essential hypertension,Zhonghua Xinxueguangbing Zazhi(Chinese Journal of Cardiology),44(7):594-599(陈鋆,龚逸炜,周晓琴,许宏勋,杨磊,吴茵茵,2016,腺苷酸环化酶3基因多态性与原发性高血压的关联研究,中华心血管病杂志,44(7):594-599)
Chen Y.L.,2011,The association of STK39,OXSR1 and SLC12A3 with essential hypertension in northeast Han Chinese,Dissertation for Ph.D.,Chinese Medical Sciences University,Supervisor:Hu J.,pp.31-32(陈艳丽,2011,STK39、OXSR1、SLC12A3与中国东北地区汉族人群高血压相关性的研究,博士学位论文,中国医科大学,导师:胡健,pp.31-32)
Chen Y.Q.,Xu W.,Wu J.L.,Gan T.,Chen X.M.,Liao X.Q.,and Chen S.Q.,2015,Association of Foxp3 gene polymorphisms with essential hypertension,Shiyong Yixue Zazhi(The Journal of Practical Medicine),31(22):3723-372(陈永权,许卫,伍金雷,甘婷,陈晞明,廖雪琼,陈盛强,2015,Foxp3基因多态性与原发性高血压的相关性,实用医学杂志,31(22):3723-3726)
Chen Z.L.,He L.J.,Zhang X.W.,Sun Q.K.,Li C.H.,Sun X.L.,Chen W.K.,Huang Q.X.,and Huang X.J.,2015,Clinical characteristics and SLC12A3 gene mutation analysis of a patient with Gitelman syndrome,Zhonghua Neifengmi Daixie Zazhi(Chinese Journal of Endocrinology and Metabolism),31(10):910-912(陈占玲,何灵杰,张秀薇,孙庆凯李春华,孙晓玲,陈伟坤,黄秋霞,黄秀娟,2015,一例Gitelman综合征患者临床资料与SLC12A3基因突变分析研究,中华内分泌代谢杂志,31(10):910-912)
Gao C.L.,Ma S.R.,Xia Z.K.,Gao Y.F.,Fan Z.M.,Xu M.,Wei W.,Zhou Y.,and Mo G.L.,2015,The study of SLC12A3complicated heterozygotic mutation in Children Gitelman syndrome,Yixue Yanjiusheng Xuebao(Journal of Medical Postgraduates),3(1):37-40(高春林,马上茹,夏正坤,高远赋,樊忠民,徐敏,魏伟,周昱,莫桂玲,2015,儿童Gitelman综合征的SLC12A3基因复杂杂合突变,医学研究生学报,3(1):37-40)
Haffner S.M.,Lehto S.,R觟nnemaa T.,Py觟r覿l覿K.,and Laakso M.,1998,Mortality from coronary heart disease in subjects with type 2 diabetes and in nondiabetic subjects with and without prior myocardial infarction,Engl.J.Med.,339(4):229-234
Jung J.,and Lee M.,2017,Effects of interaction between SLC12A3 polymorphism,salt-sensitive gene,and sodium intake on risk of child obesity,Journal of Nutrition&Health,50(1):32-40
Kosugi T.,Nakagawa T.,Kamath D.,and Johnson R.J.,2009,Uric acid and hypertension:an age-related relationship?J.Hum.Hypertens.,23(2):75-76
Lee J.H.,O'Keefe J.H.,Bell D.,Hensrud D.D.,and Holick M.F.,2008,Vitamin D deficiency an important,common,and eas ily treatable cardiovascular risk factor?J.Am.Coll.Cardiol.,52(24):1949-1956
Liang J.Q.,Xi Y.G.,An C.Y.,and Su X.L.,2015,Association of variants in renal salt reabsorption-related gene SLC12A3with essential hypertension in a Mongolian population,Genet.Mol.Res.,14(3):10026-10036
Liang Y.J.,2011,Prospective cohort on predictive risk of childhood hypertension to hypertension and subclinical target organ damages in adults,Dissertation for Ph.D.,Beijing A-cademy of Medical Sciences(Chinese Academy of Medical Sciences),Supervisor:Mi J.,pp.4-6(梁亚军,2011,儿童期高血压预测成年高血压及靶器官损害的前瞻性研究,博士学位论文,北京协和医学院(中国医学科学院),导师:米杰,pp.4-6)
Liu X.J.,2016,Research and prevention of younger age causes of hypertension,Zhongxiyi Jiehe Xinxueguanbing Dianzi Zazhi(Cardiovascular Disease Journal of Integrated Traditional Chinese and Western Medicine(Electronic)),4(18):26-27(柳晓江,2016,高血压低龄化原因与预防探究,中西医结合心血管病电子杂志,4(18):26-27)
Ma Y.H.,Chen C.,Yue Y.X.,Zhong J.F.,Chen W.J.,Lu X.L.,Huang J.Y.,and Liu C.Z.,2015,Association study between KCNE2 rs10854373 polymorphism and genetic susceptibility of coronary artery disease,Guangdong Yixue(Guangdong Medical Journal),36(15):2353-2355(马月华,陈灿,岳玉霞,钟剑锋,陈文江,卢新林,黄家园,刘长召,2015,KCNE2基因rs10854373多态位点与冠心病遗传易感性的关系,广东医学,36(15):2353-2355)
Oparil S.,Zaman M.A.,and Calhoun D.A.,2003,Pathogenesis of hypertension,Ann.Intern.Med.,139(9):761-776
Rahmouni K.,Correia M.L.G.,Haynes W.G.,and Mark A.L.,2005,Obesity-associated hypertension,Hypertension,45(1):9-14
Segura J.,and Ruilope L.M.,2007,Obesity,essential hypertension and renin-angiotensin system,Public Health Nutr.,10(10A):1151-1155
Shi Q.P.,Zhang Y.,Wang H.,Youyang J.Y.,Chen F.,and Xu M.,2015,Association of cystathionineβ-synthase gene polymorphisms with essential hypertension in ethnic Uyghurs and Hans from Xinjiang,Zhonghua Yixue Yichuanxue Za zhi(Chinese Journal of Medical Genetics),32(1):94-100(时庆平,张颖,王红,欧阳菊艳,陈芳,许梦,2015,新疆维吾尔族,汉族胱硫醚β-合成酶基因多态性及血浆同型半胱氨酸与原发性高血压的相关性,中华医学遗传学杂志,32(1):94-100)
Wu C.Y.,Zhou X.M.,Dong M.,Huang K.Q.,Xu H.,Su Y.,Wang L.,Chen X.G.,and Zhang H.M.,2015,Correlation between AT1R gene polymorphism and environmental factors and its implication for TCM patterns in essential hypertension,Beijin Zhongyiyao Daxue Xuebao(Journal of Beijing University of Traditional Chinese Medicine),38(12):817-822(吴传云,周雪梅,董梅,黄开泉,徐慧,苏瑀,汪莉,陈雪功,张红梅,2015,AT1R基因位点与环境因素交互作用对原发性高血压证候形成的影响,北京中医药大学学报,38(12):817-822)
Yi Y.H.,2016,Mongolia SLC12A3 genes(Rs11644728,Rs5803)polymorphism and coronary heart disease susceptibility study,Thesis for M.S.,Inner Mongolia Medical University,Supervisors:Wang L.P.,and Zhao N.J.,pp.13-15(尹永厚,2016,蒙古族SLC12A3基因(Rs11644728,Rs5803)多态性与冠心病发生易感研究,硕士学位论文,内蒙古医科大学,导师:王立平和赵能君,pp.13-15)
Zhang G.P.,He N.,Cong M.Y.,Zhang K.Y.,Li J.P.,Zhao J.B.,and Qiu C.C.,2017,The interaction effect of renin gene MboI polymorphism and environmental factors in essential hypertension,Zhonghua Jibing Kongzhi Zazhi(Chinese Journal of Disease Control&Prevention),21(5):473-477(张国平,何宁,丛明宇,张可勇,李静平,赵景波,邱长春,2017,肾素基因MboI多态性与环境因素交互作用对原发性高血压的影响,中华疾病控制杂志,21(5):473-477)
Zhang Y.,Han D.F.,and Zhang X.N.,Correlation between PCSK9 gene rs529787 polymorphism and blood lipid and ischemic stroke,Zhongguo Quanke Yixue(Chinese General Practice),19(7):803-807(张艳,韩登峰,张小宁,2016,前蛋白转化酶枯草溶菌素9基因rs529787位点多态性与血脂和缺血性脑卒中的关系研究,中国全科医学,19(7):803-807)
Zhu J.,Yuan X.L.,Zhang M.N.,Li Y.,Cheng X.Y.,Li H.,and Qu S.,2016,Clinical features and genetic analysis of three patients with Gitelman syndrome,Zhonghua Neifengmi Daixie Zazhi(Chinese Journal of Endocrinology and Metabolism),32(7):590-593(祝洁,袁晓岚,张曼娜,李妍,程晓芸,李鸿,曲伸,2016,三例Gitelman综合征患者临床特点及基因突变分析,中华内分泌代谢杂志,32(7):590-593)
Burt V.L.,Whelton P.,Roccella E.J.,Brown C.,Cutler J.A.,Higgins M.,Horan M.J.,and Labarthe D.,1995,Prevalence of hypertension in the US adult population:results from the third national health and nutrition examination survey,1988-1991,Hypertension,25(3):305-313
Carretero O.A.,and Oparil S.,2000,Essential hypertension.Part I:definition and etiology,Circulation,101(3):329-335
Chen F.,Zhang Y.,Wang H.,Youyang J.Y.,Munila·Ainiwaer,Kalibinuer·Yakefu,and Yang M.Z.,2015,Association of plasma homocysteine level and polymorphism of methione synthase reductase gene with essential hypertension in ethnic Uyghurs and Hans from Xinjiang,Zhonghua Yixue Yichuangxue Zazhi(Chinese Journal of Medical Genetics),32(4):548-553(陈芳,张颖,王红,欧阳菊艳,木尼拉·艾尼瓦尔,卡丽比努尔·雅合甫,杨梦智,2015,同型半胱氨酸水平及其MSR基因多态性与新疆维吾尔族、汉族原发性高血压的相关性,中华医学遗传学杂志,32(4):548-553)
Chen Y.,Gong Y.W.,Zhou X.Q.,Xu H.X.,Yang L.,and Wu Y.Y.,2016,Association between single nucleotide polymorphism of adenylyl cyclase 3 and essential hypertension,Zhonghua Xinxueguangbing Zazhi(Chinese Journal of Cardiology),44(7):594-599(陈鋆,龚逸炜,周晓琴,许宏勋,杨磊,吴茵茵,2016,腺苷酸环化酶3基因多态性与原发性高血压的关联研究,中华心血管病杂志,44(7):594-599)
Chen Y.L.,2011,The association of STK39,OXSR1 and SLC12A3 with essential hypertension in northeast Han Chinese,Dissertation for Ph.D.,Chinese Medical Sciences University,Supervisor:Hu J.,pp.31-32(陈艳丽,2011,STK39、OXSR1、SLC12A3与中国东北地区汉族人群高血压相关性的研究,博士学位论文,中国医科大学,导师:胡健,pp.31-32)
Chen Y.Q.,Xu W.,Wu J.L.,Gan T.,Chen X.M.,Liao X.Q.,and Chen S.Q.,2015,Association of Foxp3 gene polymorphisms with essential hypertension,Shiyong Yixue Zazhi(The Journal of Practical Medicine),31(22):3723-372(陈永权,许卫,伍金雷,甘婷,陈晞明,廖雪琼,陈盛强,2015,Foxp3基因多态性与原发性高血压的相关性,实用医学杂志,31(22):3723-3726)
Chen Z.L.,He L.J.,Zhang X.W.,Sun Q.K.,Li C.H.,Sun X.L.,Chen W.K.,Huang Q.X.,and Huang X.J.,2015,Clinical characteristics and SLC12A3 gene mutation analysis of a patient with Gitelman syndrome,Zhonghua Neifengmi Daixie Zazhi(Chinese Journal of Endocrinology and Metabolism),31(10):910-912(陈占玲,何灵杰,张秀薇,孙庆凯李春华,孙晓玲,陈伟坤,黄秋霞,黄秀娟,2015,一例Gitelman综合征患者临床资料与SLC12A3基因突变分析研究,中华内分泌代谢杂志,31(10):910-912)
Gao C.L.,Ma S.R.,Xia Z.K.,Gao Y.F.,Fan Z.M.,Xu M.,Wei W.,Zhou Y.,and Mo G.L.,2015,The study of SLC12A3complicated heterozygotic mutation in Children Gitelman syndrome,Yixue Yanjiusheng Xuebao(Journal of Medical Postgraduates),3(1):37-40(高春林,马上茹,夏正坤,高远赋,樊忠民,徐敏,魏伟,周昱,莫桂玲,2015,儿童Gitelman综合征的SLC12A3基因复杂杂合突变,医学研究生学报,3(1):37-40)
Haffner S.M.,Lehto S.,R觟nnemaa T.,Py觟r覿l覿K.,and Laakso M.,1998,Mortality from coronary heart disease in subjects with type 2 diabetes and in nondiabetic subjects with and without prior myocardial infarction,Engl.J.Med.,339(4):229-234
Jung J.,and Lee M.,2017,Effects of interaction between SLC12A3 polymorphism,salt-sensitive gene,and sodium intake on risk of child obesity,Journal of Nutrition&Health,50(1):32-40
Kosugi T.,Nakagawa T.,Kamath D.,and Johnson R.J.,2009,Uric acid and hypertension:an age-related relationship?J.Hum.Hypertens.,23(2):75-76
Lee J.H.,O'Keefe J.H.,Bell D.,Hensrud D.D.,and Holick M.F.,2008,Vitamin D deficiency an important,common,and eas ily treatable cardiovascular risk factor?J.Am.Coll.Cardiol.,52(24):1949-1956
Liang J.Q.,Xi Y.G.,An C.Y.,and Su X.L.,2015,Association of variants in renal salt reabsorption-related gene SLC12A3with essential hypertension in a Mongolian population,Genet.Mol.Res.,14(3):10026-10036
Liang Y.J.,2011,Prospective cohort on predictive risk of childhood hypertension to hypertension and subclinical target organ damages in adults,Dissertation for Ph.D.,Beijing A-cademy of Medical Sciences(Chinese Academy of Medical Sciences),Supervisor:Mi J.,pp.4-6(梁亚军,2011,儿童期高血压预测成年高血压及靶器官损害的前瞻性研究,博士学位论文,北京协和医学院(中国医学科学院),导师:米杰,pp.4-6)
Liu X.J.,2016,Research and prevention of younger age causes of hypertension,Zhongxiyi Jiehe Xinxueguanbing Dianzi Zazhi(Cardiovascular Disease Journal of Integrated Traditional Chinese and Western Medicine(Electronic)),4(18):26-27(柳晓江,2016,高血压低龄化原因与预防探究,中西医结合心血管病电子杂志,4(18):26-27)
Ma Y.H.,Chen C.,Yue Y.X.,Zhong J.F.,Chen W.J.,Lu X.L.,Huang J.Y.,and Liu C.Z.,2015,Association study between KCNE2 rs10854373 polymorphism and genetic susceptibility of coronary artery disease,Guangdong Yixue(Guangdong Medical Journal),36(15):2353-2355(马月华,陈灿,岳玉霞,钟剑锋,陈文江,卢新林,黄家园,刘长召,2015,KCNE2基因rs10854373多态位点与冠心病遗传易感性的关系,广东医学,36(15):2353-2355)
Oparil S.,Zaman M.A.,and Calhoun D.A.,2003,Pathogenesis of hypertension,Ann.Intern.Med.,139(9):761-776
Rahmouni K.,Correia M.L.G.,Haynes W.G.,and Mark A.L.,2005,Obesity-associated hypertension,Hypertension,45(1):9-14
Segura J.,and Ruilope L.M.,2007,Obesity,essential hypertension and renin-angiotensin system,Public Health Nutr.,10(10A):1151-1155
Shi Q.P.,Zhang Y.,Wang H.,Youyang J.Y.,Chen F.,and Xu M.,2015,Association of cystathionineβ-synthase gene polymorphisms with essential hypertension in ethnic Uyghurs and Hans from Xinjiang,Zhonghua Yixue Yichuanxue Za zhi(Chinese Journal of Medical Genetics),32(1):94-100(时庆平,张颖,王红,欧阳菊艳,陈芳,许梦,2015,新疆维吾尔族,汉族胱硫醚β-合成酶基因多态性及血浆同型半胱氨酸与原发性高血压的相关性,中华医学遗传学杂志,32(1):94-100)
Wu C.Y.,Zhou X.M.,Dong M.,Huang K.Q.,Xu H.,Su Y.,Wang L.,Chen X.G.,and Zhang H.M.,2015,Correlation between AT1R gene polymorphism and environmental factors and its implication for TCM patterns in essential hypertension,Beijin Zhongyiyao Daxue Xuebao(Journal of Beijing University of Traditional Chinese Medicine),38(12):817-822(吴传云,周雪梅,董梅,黄开泉,徐慧,苏瑀,汪莉,陈雪功,张红梅,2015,AT1R基因位点与环境因素交互作用对原发性高血压证候形成的影响,北京中医药大学学报,38(12):817-822)
Yi Y.H.,2016,Mongolia SLC12A3 genes(Rs11644728,Rs5803)polymorphism and coronary heart disease susceptibility study,Thesis for M.S.,Inner Mongolia Medical University,Supervisors:Wang L.P.,and Zhao N.J.,pp.13-15(尹永厚,2016,蒙古族SLC12A3基因(Rs11644728,Rs5803)多态性与冠心病发生易感研究,硕士学位论文,内蒙古医科大学,导师:王立平和赵能君,pp.13-15)
Zhang G.P.,He N.,Cong M.Y.,Zhang K.Y.,Li J.P.,Zhao J.B.,and Qiu C.C.,2017,The interaction effect of renin gene MboI polymorphism and environmental factors in essential hypertension,Zhonghua Jibing Kongzhi Zazhi(Chinese Journal of Disease Control&Prevention),21(5):473-477(张国平,何宁,丛明宇,张可勇,李静平,赵景波,邱长春,2017,肾素基因MboI多态性与环境因素交互作用对原发性高血压的影响,中华疾病控制杂志,21(5):473-477)
Zhang Y.,Han D.F.,and Zhang X.N.,Correlation between PCSK9 gene rs529787 polymorphism and blood lipid and ischemic stroke,Zhongguo Quanke Yixue(Chinese General Practice),19(7):803-807(张艳,韩登峰,张小宁,2016,前蛋白转化酶枯草溶菌素9基因rs529787位点多态性与血脂和缺血性脑卒中的关系研究,中国全科医学,19(7):803-807)
Zhu J.,Yuan X.L.,Zhang M.N.,Li Y.,Cheng X.Y.,Li H.,and Qu S.,2016,Clinical features and genetic analysis of three patients with Gitelman syndrome,Zhonghua Neifengmi Daixie Zazhi(Chinese Journal of Endocrinology and Metabolism),32(7):590-593(祝洁,袁晓岚,张曼娜,李妍,程晓芸,李鸿,曲伸,2016,三例Gitelman综合征患者临床特点及基因突变分析,中华内分泌代谢杂志,32(7):590-593)