αENaC基因四个单核苷酸多态性与新疆哈萨克族人原发性高血压及血电解质的相关性研究
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摘要
目的：研究αENaC基因第2内含子区T3593C、第13外显子区T663A、启动子区G2139A和G3091A四个位点单核苷酸多态性(Single nucleotide polymorphisms；SNPs)、T3593C与T663A两个位点SNPs组成的联合基因型以及上述四个位点SNPs构成的单体型在新疆哈萨克族人群中的分布特点，探讨αENaC基因四个位点SNPs及T3593C与T663A两个位点SNPs组成的联合基因型、四个位点单体型与新疆哈萨克族人原发性高血压(Essential hypertension；EH)及血电解质水平的相关性。方法：采用整群抽样随机抽取的方式，以生活在新疆塔城地区和丰县、伊犁地区新源县、阿勒泰地区福海县和富蕴县30岁以上的500余名哈萨克族牧民为研究对象，进行标准化的问卷调查、体格检查。按照2005年中国高血压防治指南的高血压诊断标准，以收缩压(Systolic blood pressure；SBP)均值≥140mmHg和／或舒张压(Diastolicblood pressure；DBP)均值≥90mmHg及正在服用降压药物者为高血压组(EH组)，以SBP<140mmHg和DBP<90mmHg者为血压正常(Normotensive)的对照组(NT组)。采用基因组DNA提取试剂盒提取外周血白细胞基因组DNA，应用聚合酶链反应0限制性片断长度多态性(Polymerase chain reaction-Restriction fragment lengthpolymorphism；PCR-RFLP)方法，检测研究对象的αENaC基因T3593C、T663A、G2139A、G3091A多态位点的基因型。通过SPSS15．0统计学软件和SNPalyze软件分析新疆哈萨克族人EH组和NT组中上述多态位点各基因型、等位基因、T3593C与T663A两个位点联合基因型、四个多态位点单体型的频率分布特点，比较上述四个SNPs各基因型及不同联合基因型与新疆哈萨克族人EH和血电解质的关系，比较上述单体型中的不同组合与新疆哈萨克族人EH的相关性。结果：1)新疆哈萨克族人存在αENaC基因第2内含子区T3593C位点多态性，有TT、TC、CC三种基因型和T、C两种等位基因。三种基因型的分布频率分别为88．39％、10．63％、0．98％，两种等位基因的分布频率分别为93．7％、6．3％，基因型的分布符合Hardy-Weinberg平衡(x~2=5．03，P=0．08)。在EH组和NH组中，三种基因型的分布频率分别为89．33％、9．88％、0．79％和87．45％、11．37％、1．18％，两种等位基因的分布频率分别为94．36％、5．64％和93．14％、6．86％，三种基因型和两种等位基因在两组间的分布频率均无统计学差异(x~2=0．51，P=0．78；x~2=0．55，P=0．46)。进一步按照性别(男性与女性)、体重指数(体重正常：BMI<24Kg／m~2；超重肥胖：BMI≥24Kg／m~2)、年龄(≤39岁，40～49岁，≥50岁)分层分析后，发现不同性别、不同体重指数、不同年龄阶段研究对象的三种基因型和两种等位基因在EH组NH组间的分布频率均无统计学差异(P>0．05)。携带TT与TC+CC基因型研究对象的血压及血电解质各水平间的差异均无统计学意义(P>0．05)。多元Logistic回归分析在控制了年龄、性别、BMI等混杂因素后显示T3593C多态性仍不是新疆哈萨克族人EH的独立危险因素，且与该民族的血电解质水平不相关。2)新疆哈萨克族人存在αENaC基因第13外显子区T663A位点多态性，有AA、AG、GG三种基因型和A、G两种等位基因。三种基因型的分布频率分别为15．7％、50．2％、34．1％，两种等位基因的分布频率分别为40．8％、59．2％，基因型的分布符合Hardy-Weinberg定律(x~2=0．79，P=0．67)。在EH组和NT组中，三种基因型的分布频率分别为16．3％、49．1％、34．6％和15．1％、51．4％、33．5％，两种等位基因的分布频率分别为40．9％、59．1％和41％、59％，三种基因型与两种等位基因在两组间的分布频率均无统计学差异(x~2=0.315，P=0．854；x~2=0．002，P=1．0)。进一步按照性别(男性与女性)、体重指数(体重正常：BMI<24Kg／m~2；超重肥胖：BMI≥24Kg／m~2)、年龄(≤39岁，40～49岁，≥50岁)分层分析后，发现不同性别、不同体重指数、不同年龄阶段研究对象的三种基因型和两种等位基因在EH组NH组间的分布频率均无统计学差异(P>0．05)。携带T663A位点AA基因型研究对象的血Na~+水平高于基因型AG、GG的(P=0．032)，但三种基因型间研究对象的血压及K~+水平间不存在统计学差异(P>0．05)。多元Logistic回归分析在控制了年龄、性别、BMI等混杂因素后认为T663A多态性不是新疆哈萨克族人EH的独立危险因素。3)新疆哈萨克族人存在αENaC基因启动子区G2139A位点多态性，有AA、AG、GG三种基因型及A、G两种等位基因。三种基因型的分布频率分别为25．88％、51．95％、22．17％，两种等位基因的分布频率分别为51．85％、48．15％，基因型的分布符合Hardy-Weinberg平衡(x~2=0．84，P=0．66)。在EH组和NT组中，三种基因型的分布频率分别为25．1％、52．1％、22.8％和26．70％、51．8％、21．6％，A、G两种等位基因的分布频率分别为51．16％、48．84％和52．55％、47．45％，三种基因型和两种等位基因在两组间的分布频率均不存在统计学差异(x~2=0．211，P=0．900；x~2=0．199，P=0．663)。进一步按照性别(男性与女性)、体重指数(体重正常：BMI<24Kg／m~2；超重肥胖：BMI≥24Kg／m~2)、年龄(≤39岁，40～49岁，≥50岁)分层分析后，发现不同性别、不同体重指数、不同年龄阶段研究对象的三种基因型和两种等位基因在EH组NH组间的分布频率均无统计学差异(P>0．05)。三种基因型间、进一步将基因型进行合并及在较年轻人群中(年龄≤55岁)，未发现G2139A多态位点各基因型携带者间的血压及血电解质水平存在统计学差异(P>0．05)。多元Logistic回归分析在控制了年龄、性别、BMI等混杂因素后显示G2139A多态性仍不是新疆哈萨克族人EH的独立危险因素，且与该民族的血电解质水平不相关。4)新疆哈萨克族人存在αENaC基因启动子区G3091A位点多态性，有AA、AG、GG三种基因型及A、G两种等位基因。三种基因型的分布频率分别为19．4％、51．3％、28％，两种等位基因的分布频率分别为45．6％、54．4％，基因型的分布符合Hardy-Weinberg平衡(x~2=1．21，P=0．55)。在EH组和NT组中，三种基因型的分布频率分别为19．7％、52．1％、28．2％和19．5％、51．9％、28．6％，两种等位基因的分布频率分别为45．8％、54．2％和45．5％、54．5％，三种基因型和两种等位基因在两组间的分布频率均不存在统计学差异(x~2=0．01，P=0．99；x~2=0．007，P=0．93)。进一步按照性别(男与女)、体重指数(体重正常：BMI<24Kg／m~2；超重肥胖：BMI≥24Kg/m~2)、年龄(≤39岁，40～49岁，≥50岁)分层分析后，发现不同性别、不同体重指数、不同年龄阶段研究对象的三种基因型和两种等位基因在EH组NH组间的分布频率均无统计学差异(P>0．05)。该多态位点三种基因型携带者间在血压及血电解质各水平差异均无统计学意义(P>0．05)。多元Logistic回归分析在控制了年龄、性别、BMI等混杂因素后显示G3091A多态性仍不是新疆哈萨克族人EH的独立危险因素，且与该民族的血电解质水平不相关。5)本研究第一部分的资料显示新疆哈萨克族人αENaC基因T3593C、T663A、G2139A和G3091A位点EH组研究对象的K~+、Na~+水平均显著高于NT组，而Na~+／K~+水平则均较NT组研究对象显著降低(P<0．05)。6)T663A与T3593C 2个位点多态性共组成9种联合基因型，未发现在NT组和EH组间9种联合基因型的分布频率存在统计学差异(x~2=6．449，P=0．597)。携带T663A GG与T3593C TT联合基因型研究对象的Na~+水平低于其他各联合基因型(P=0．03)。不同组合联合基因型研究对象间的血压水平不存在统计学差异(P>0．05)。多元Logistic回归分析在控制了年龄、性别、BMI等混杂因素后，认为T663A与T3593C位点多态性组成的联合基因型不是新疆哈萨克族人EH的独立危险因素，但T663A GG与T3593C TT联合基因型与该民族血Na~+水平的变化有关。7)新疆哈萨克族人群αENaC基因G2139A、G3091A、T663A和T3593C四个SNPs之间不存在连锁不平衡关系，共构成数十种单体型。单体型分析发现2139G、3091A、663G、3593T等位基因构成的H1单体型的分布频率在EH组中明显升高，与NT组相比差异有统计学意义(在EH组，NT组中的分布频率分别为82．5％，71％；x~2=7．41，P=6．482E-3)，2139A、3091A、663A、3593C等位基因构成的H2单体型的分布频率在EH组中明显降低，与NT组相比差异有显著性(在EH组与NT组中的分布频率分别为8．5％，16％，x~2=5．23，P=0．022)。结论：1)本研究资料显示在四个SNPs中，EH组研究对象的K~+、Na~+水平均显著高于NT组，而Na~+／K~+水平则均较NT组研究对象显著降低。2)新疆哈萨克族人群αENaC基因存在T3593C、T663A、G2139A、G3091A位点多态性。T663A位点、G2139A位点、G3091A位点均存在AA、AG、GG三种基因型和A、G两种等位基因；T3593C位点存在TT、TC、CC三种基因型和T、C两种等位基因。3)除T663A基因型AA可能与该民族血Na~+水平升高相关外，新疆哈萨克族人αENaC基因T3593C、G2139A、G3091A三个SNPs可能与该民族EH的发生及血电解质水平均不相关。4)T663A GG与T3593C TT联合基因型可能影响新疆哈萨克族人的血Na~+水平。而T663A与T3593C位点多态组成的9种联合基因型可能与该民族EH的发生不相关。5)G2139A、G3091A、T663A和T3593C四个SNPs构成的数十种单体型结果分析提示2139G、3091A、663G、3593T等位基因构成的H1单体型可能与新疆哈萨克族人EH的发生相关，而2139A、3091A、663A、3593C等位基因构成的H2单体型可能可降低该民族EH的患病风险。6)通过αENaC基因四个SNPs与EH及血电解质的相关性研究发现ENaC基因作为盐敏感基因是新疆哈萨克族人EH易感的重要的候选基因之一。
Objective: To investigate distributed characteristic of the T3593C, T663A, G2139A, G3091A single nucleotide polymorphisms (SNPs) ofαENaC gene which located at the second intron, the 13th exon region and the promoter region in a subunit gene of epithelial sodium channel (ENaC), respectively, the united genotypes of T3593C and T663A and the haplotypes composed by the G2139A, T663A, G3091A T3593C in Xinjiang Kazakhs. And to research the relationship between four SNPs and the united genotypes with essential hypertension (EH) and serum electrolytes and the association between the haplotypes with EH of Xinjiang Kazakhs. Methods: More than 500 Xinjiang Kazakhs aged more than 30 years old were recruited in this population based on case-control study by cluster sampling who lived in pasture area of Hefen, Xinyuan, Fuhai and Fuyun county in Xinjiang. After questionnaire and physical examination, they were divided into hypertensives (EH group) whose systolic blood pressure (SBP) were≥140mmHg and/or diastolic blood pressure (DBP) were≥90mmHg and normotensives (NT group) whose blood pressure were < 140/90mmHg according to the guideline of the hypertensive prevention and treatment of China in 2005. We extracted the genome DNA of peripheral leucocyte by kits and measured their gene polymorphisms of T3593C, T663A, G2139A, G3091A by Polymerase chain reaction-Restriction fragment length polymorphism (PCR-RFLP) method. We studied the relationship of the polymorphisms and the united genotypes with EH and serum electrolytes and researched the association of the haplotypes with EH by SPSS 15.0 statistic software and SNPalyze software.
Results:1) Three kinds of genotypes and two kinds of alleles of aENaC gene T3593C polymorphism were detected in Xinjiang Kazakhs. In this population, the frequencies of the genotypes TT, TC, CC were 88.39%, 10.63%, 0.98% and the frequencies of alleles T, C were 93.7%, 6.3%, respectively. The genotypic frequencies were in Hardy-Weinberg equilibrium (x~2=5.03, P=0.08). The distributed genotypic frequencies of TT, TC, CC were 89.33%, 9.88%, 0.79% in EH group and 87.45%, 11.37%, 1.18% in NT group, respectively. The distributed allelic frequencies of T, C were 94.36%, 5.64% in EH group and 93.14%, 6.86% in NT group, respectively. The distribution of genotypic and allelic frequencies had no significant difference between EH group and NH group (x~2=0.51, P=0.78; x~2=0.55, P=0.46). Through to analyze the data stratified with gender (male and female), BMI (normoweight: BMI<24Kg/m~2; overweight: BMI≥24Kg/m~2), different age groups (≤39 years old, 40-49 years old,≥50 years old), the distribution of genotypic and allelic frequencies had no significant difference between two groups (P> 0.05). There was no significant difference in levels of blood pressure and serum electrolytes between subjects with the TT and TC+CC genotypes (P>0.05). The genotypes of the T3593C polymorphism were excluded as independent variables which related to the blood pressure and serum electrolytes of subjects after controlling the confounding factors like age, gender, BMI by multiple logistic analysis. 2) We detected three kinds of genotypes and two kinds of alleles of aENaC gene T663 A polymorphism in Xinjiang Kazakhs. The genotypic frequencies of the AA, AG, GG were 15.7%, 50.2%, 34.1% and the allelic frequencies of A, G were 40.8%, 59.2%, respectively. The distributed genotypic frequencies were in Hardy-Weinberg equilibrium ( x~2 =0.79, P=0.67). The distributed genotypic frequencies of AA, AG, GG were 16.3%, 49.1%, 34.6% in EH group and 15.1%, 51.4%, 33.5% in NT group, respectively. The distributed allelic frequencies of A, G were 40.9%, 59.1% in EH group and 41%, 59% in NT group, respectively. Both of genotypic and allelic frequencies had no significant difference between EH group and NH group (x~2 =0.315, P=0.854; x~2 =0.002, P=1.0). Through to analyze the data stratified with gender (male and female), BMI (normoweight: BMK 24Kg/m~2 ; overweight: BMI≥24Kg/m~2), different age groups (≤39 years old, 40-49 years old,≥50 years old), the distribution of genotypic and allelic frequencies had no significant difference between two groups (P>0.05). There was no significant difference in level of blood pressure among subjects with the three kinds of genotypes (P>0.05). But the serum Na~+ of the subjects with AA genotype was higher than those subjects with AG and GG genotypes (P=0.032). The genotypes of the T663A polymorphism were excluded as independent variables relating to EH after controlling the mixed factors of age, gender, BMI by multiple logistic analysis. 3) We detected three kinds of genotypes and two kinds of alleles of G2139A polymorphism in Xinjiang Kazakhs. The genotypic frequencies of AA, AG, GG were 25.88%, 51.95%, 22.17% and the allelic frequencies of A, G were 51.85%, 48.15%, respectively. The genotypic frequencies were in Hardy-Weinberg equilibrium (x~2 =0.84, P=0.66). The distributed genotypic frequencies of AA, AG, GG were 25.1%, 52.1%, 22.8% in EH group and 26.70%, 51.8%, 21.6% in NT group, respectively. The distributed allelic frequencies of A, G were 51.16%, 48.84% in EH group and 52.55%, 47.45% in NT group, respectively. The distribution of genotypic and allelic frequencies had no significant difference between these two groups (x~2 =0.211, P=0.900; x~2 =0.199, P=0.663) ). Through to analyze the data stratified with gender (male and female ), BMI (normoweight: BMK24Kg/m2; overweight: BMI≥24Kg/m~2), different age groups (≤39 years old, 40-49 years old,≥50 years old), the distribution of genotypic and allelic frequencies had no significant difference between these two groups (P>0.05). The genotypes of the G2139A polymorphism were excluded as independent variables which related to the blood pressure and serum electrolytes among subjects after controlling the confounding factors like age, gender, BMI by multiple logistic analysis. 4) We detected three kinds of genotypes and two kinds of alleles of G3091A polymorphism in Xinjiang Kazakhs. The frequencies of the genotypes AA, AG, GG were 19.4%, 51.3%, 28% and the frequencies of alleles A, G were 45.6%, 54.4%, respectively, the genotypic frequencies were in Hardy-Weinberg equilibrium (x~2=1.21, P=0.55). The distributed genotypic frequencies of AA, AG, GG were 19.7%, 52.1%, 28.2% in EH group and 19.5%, 51.9%, 28.6% in NT group, respectively. The distributed allelic frequencies of A , G were 45.8%, 54.2% in EH group and 45.5%, 54.5% in NT group, respectively. The distribution of genotypic and allelic frequencies had no significant difference between these two groups (x~2=0.01, P=0.99; x~2 =0.007, P=0.93). Through to analyze the data stratified with gender (male and female ), BMI (normoweight: BMI<24Kg/m~2; overweight: BMI≥24Kg/m~2), different age groups (≤39 years old, 40-49 years old,≥50 years old), the distribution of genotypic and allelic frequencies had no significant difference between these two groups (P>0.05). The genotypes of G3091A polymorphism were excluded as independent variables which related to the blood pressure and serum electrolytes of subjects after controlling the confounding factors like age, gender, BMI by multiple logistic analysis. 4) Nine kinds of united genotypes were composed by T3593C and T663A polymorphisms. The distribution of the united genotypic frequencies had no significant difference between EH group and NT group (x~2 =6.449, P=0.597). There was no significant difference in level of blood pressure among subjects with the different united genotypes (P>0.05). But the serum Na~+ of the subjects with the united genotype composed by T663A AA and T3593C TT was lower than those subjects with the other united genotypes (P=0.03). And the genotypes of the united genotypes were excluded as independent variables which related to the blood pressure among subjects after controlling the confounding factors like age, gender, BMI by multiple logistic analysis. 5) The results of the first parts showed the serum K~+, Na~+ in EH group were higher but the Na~+/K~+ were lower than those in the NT group (P<0.05). 6)There were no linkage disequilibrium among G2139A, G3091A, T663A, T3593C. There were more than ten kinds of haplotypes were constituted by these four SNPs in Xinjiang Kazakhs. There were significant difference in distributed frequencies of two kinds of haplotypes between EH group and NT group. The frequency of H1 haplotype consituted by 2139G, 3091A, 663G and 3593T in EH group was significant higher than that m NT group(x~2 =7.41,P=6.482E-3), wheras the frequency of H2 haplotype composed by 2139A, 3091 A, 663A and 3593C in EH group was significant lower than that in NT group(x~2=5.23, P=0.022). Conclusions: 1) The levels of the serum K~+, Na~+ in EH group were higher but the levels of Na~+/K~+ were lower than those in NT group. 2) There existed T3593C, T663A, G2139A, G3091A polymorphisms of aENaC gene in Xinjiang Kazakhs. There were three kinds of genotypes AA, AG, GG and two kinds of alleles A, G in T663A , G2139A, G3091A polymorphisms, respectively. There were three kinds of genotypes TT, TC, CC and two kinds of alleles T, C in T3593C polymorphism. 3) Our study indicated that T3593C, G2139A and G3091A polymorphisms might not be associated with EH and serum electrolytes of Xinjiang Kazakhs except that the AA genotype of T663A polymorphisms might be associated with the higher level of the serum Na~+of Xinjiang Kazakhs. 4) The nine united genotypes composed by T663A and G3091A polymorphisms might not be associated with EH in Xinjiang Kazakhs. But the united genotypes composed by T663A GG and T3593C TT might be associated with the lower level of the serum Na~+in Xinjiang Kazakhs. 5) There were more than ten kinds of haplotypes constituted by G2139A, G3091A, T663A and T3593C. The H1 haplotype composed by the alleles with 2139G, 3091A, 663G and 3593T might be associated with EH in Xinjiang Kazakhs, however, the H2 haplotype composed by the alleles with 2139A, 3091A, 663A and 3593C might decreased the risk of EH in Xinjiang Kazakhs. 6) The salt sensitive gene --- ENaC gene are still one of the important candidate genes related to EH in Xinjiang Kazakhs.
Objective: To investigate distributed characteristic of the T3593C, T663A, G2139A, G3091A single nucleotide polymorphisms (SNPs) ofαENaC gene which located at the second intron, the 13th exon region and the promoter region in a subunit gene of epithelial sodium channel (ENaC), respectively, the united genotypes of T3593C and T663A and the haplotypes composed by the G2139A, T663A, G3091A T3593C in Xinjiang Kazakhs. And to research the relationship between four SNPs and the united genotypes with essential hypertension (EH) and serum electrolytes and the association between the haplotypes with EH of Xinjiang Kazakhs. Methods: More than 500 Xinjiang Kazakhs aged more than 30 years old were recruited in this population based on case-control study by cluster sampling who lived in pasture area of Hefen, Xinyuan, Fuhai and Fuyun county in Xinjiang. After questionnaire and physical examination, they were divided into hypertensives (EH group) whose systolic blood pressure (SBP) were≥140mmHg and/or diastolic blood pressure (DBP) were≥90mmHg and normotensives (NT group) whose blood pressure were < 140/90mmHg according to the guideline of the hypertensive prevention and treatment of China in 2005. We extracted the genome DNA of peripheral leucocyte by kits and measured their gene polymorphisms of T3593C, T663A, G2139A, G3091A by Polymerase chain reaction-Restriction fragment length polymorphism (PCR-RFLP) method. We studied the relationship of the polymorphisms and the united genotypes with EH and serum electrolytes and researched the association of the haplotypes with EH by SPSS 15.0 statistic software and SNPalyze software.
Results:1) Three kinds of genotypes and two kinds of alleles of aENaC gene T3593C polymorphism were detected in Xinjiang Kazakhs. In this population, the frequencies of the genotypes TT, TC, CC were 88.39%, 10.63%, 0.98% and the frequencies of alleles T, C were 93.7%, 6.3%, respectively. The genotypic frequencies were in Hardy-Weinberg equilibrium (x~2=5.03, P=0.08). The distributed genotypic frequencies of TT, TC, CC were 89.33%, 9.88%, 0.79% in EH group and 87.45%, 11.37%, 1.18% in NT group, respectively. The distributed allelic frequencies of T, C were 94.36%, 5.64% in EH group and 93.14%, 6.86% in NT group, respectively. The distribution of genotypic and allelic frequencies had no significant difference between EH group and NH group (x~2=0.51, P=0.78; x~2=0.55, P=0.46). Through to analyze the data stratified with gender (male and female), BMI (normoweight: BMI<24Kg/m~2; overweight: BMI≥24Kg/m~2), different age groups (≤39 years old, 40-49 years old,≥50 years old), the distribution of genotypic and allelic frequencies had no significant difference between two groups (P> 0.05). There was no significant difference in levels of blood pressure and serum electrolytes between subjects with the TT and TC+CC genotypes (P>0.05). The genotypes of the T3593C polymorphism were excluded as independent variables which related to the blood pressure and serum electrolytes of subjects after controlling the confounding factors like age, gender, BMI by multiple logistic analysis. 2) We detected three kinds of genotypes and two kinds of alleles of aENaC gene T663 A polymorphism in Xinjiang Kazakhs. The genotypic frequencies of the AA, AG, GG were 15.7%, 50.2%, 34.1% and the allelic frequencies of A, G were 40.8%, 59.2%, respectively. The distributed genotypic frequencies were in Hardy-Weinberg equilibrium ( x~2 =0.79, P=0.67). The distributed genotypic frequencies of AA, AG, GG were 16.3%, 49.1%, 34.6% in EH group and 15.1%, 51.4%, 33.5% in NT group, respectively. The distributed allelic frequencies of A, G were 40.9%, 59.1% in EH group and 41%, 59% in NT group, respectively. Both of genotypic and allelic frequencies had no significant difference between EH group and NH group (x~2 =0.315, P=0.854; x~2 =0.002, P=1.0). Through to analyze the data stratified with gender (male and female), BMI (normoweight: BMK 24Kg/m~2 ; overweight: BMI≥24Kg/m~2), different age groups (≤39 years old, 40-49 years old,≥50 years old), the distribution of genotypic and allelic frequencies had no significant difference between two groups (P>0.05). There was no significant difference in level of blood pressure among subjects with the three kinds of genotypes (P>0.05). But the serum Na~+ of the subjects with AA genotype was higher than those subjects with AG and GG genotypes (P=0.032). The genotypes of the T663A polymorphism were excluded as independent variables relating to EH after controlling the mixed factors of age, gender, BMI by multiple logistic analysis. 3) We detected three kinds of genotypes and two kinds of alleles of G2139A polymorphism in Xinjiang Kazakhs. The genotypic frequencies of AA, AG, GG were 25.88%, 51.95%, 22.17% and the allelic frequencies of A, G were 51.85%, 48.15%, respectively. The genotypic frequencies were in Hardy-Weinberg equilibrium (x~2 =0.84, P=0.66). The distributed genotypic frequencies of AA, AG, GG were 25.1%, 52.1%, 22.8% in EH group and 26.70%, 51.8%, 21.6% in NT group, respectively. The distributed allelic frequencies of A, G were 51.16%, 48.84% in EH group and 52.55%, 47.45% in NT group, respectively. The distribution of genotypic and allelic frequencies had no significant difference between these two groups (x~2 =0.211, P=0.900; x~2 =0.199, P=0.663) ). Through to analyze the data stratified with gender (male and female ), BMI (normoweight: BMK24Kg/m2; overweight: BMI≥24Kg/m~2), different age groups (≤39 years old, 40-49 years old,≥50 years old), the distribution of genotypic and allelic frequencies had no significant difference between these two groups (P>0.05). The genotypes of the G2139A polymorphism were excluded as independent variables which related to the blood pressure and serum electrolytes among subjects after controlling the confounding factors like age, gender, BMI by multiple logistic analysis. 4) We detected three kinds of genotypes and two kinds of alleles of G3091A polymorphism in Xinjiang Kazakhs. The frequencies of the genotypes AA, AG, GG were 19.4%, 51.3%, 28% and the frequencies of alleles A, G were 45.6%, 54.4%, respectively, the genotypic frequencies were in Hardy-Weinberg equilibrium (x~2=1.21, P=0.55). The distributed genotypic frequencies of AA, AG, GG were 19.7%, 52.1%, 28.2% in EH group and 19.5%, 51.9%, 28.6% in NT group, respectively. The distributed allelic frequencies of A , G were 45.8%, 54.2% in EH group and 45.5%, 54.5% in NT group, respectively. The distribution of genotypic and allelic frequencies had no significant difference between these two groups (x~2=0.01, P=0.99; x~2 =0.007, P=0.93). Through to analyze the data stratified with gender (male and female ), BMI (normoweight: BMI<24Kg/m~2; overweight: BMI≥24Kg/m~2), different age groups (≤39 years old, 40-49 years old,≥50 years old), the distribution of genotypic and allelic frequencies had no significant difference between these two groups (P>0.05). The genotypes of G3091A polymorphism were excluded as independent variables which related to the blood pressure and serum electrolytes of subjects after controlling the confounding factors like age, gender, BMI by multiple logistic analysis. 4) Nine kinds of united genotypes were composed by T3593C and T663A polymorphisms. The distribution of the united genotypic frequencies had no significant difference between EH group and NT group (x~2 =6.449, P=0.597). There was no significant difference in level of blood pressure among subjects with the different united genotypes (P>0.05). But the serum Na~+ of the subjects with the united genotype composed by T663A AA and T3593C TT was lower than those subjects with the other united genotypes (P=0.03). And the genotypes of the united genotypes were excluded as independent variables which related to the blood pressure among subjects after controlling the confounding factors like age, gender, BMI by multiple logistic analysis. 5) The results of the first parts showed the serum K~+, Na~+ in EH group were higher but the Na~+/K~+ were lower than those in the NT group (P<0.05). 6)There were no linkage disequilibrium among G2139A, G3091A, T663A, T3593C. There were more than ten kinds of haplotypes were constituted by these four SNPs in Xinjiang Kazakhs. There were significant difference in distributed frequencies of two kinds of haplotypes between EH group and NT group. The frequency of H1 haplotype consituted by 2139G, 3091A, 663G and 3593T in EH group was significant higher than that m NT group(x~2 =7.41,P=6.482E-3), wheras the frequency of H2 haplotype composed by 2139A, 3091 A, 663A and 3593C in EH group was significant lower than that in NT group(x~2=5.23, P=0.022). Conclusions: 1) The levels of the serum K~+, Na~+ in EH group were higher but the levels of Na~+/K~+ were lower than those in NT group. 2) There existed T3593C, T663A, G2139A, G3091A polymorphisms of aENaC gene in Xinjiang Kazakhs. There were three kinds of genotypes AA, AG, GG and two kinds of alleles A, G in T663A , G2139A, G3091A polymorphisms, respectively. There were three kinds of genotypes TT, TC, CC and two kinds of alleles T, C in T3593C polymorphism. 3) Our study indicated that T3593C, G2139A and G3091A polymorphisms might not be associated with EH and serum electrolytes of Xinjiang Kazakhs except that the AA genotype of T663A polymorphisms might be associated with the higher level of the serum Na~+of Xinjiang Kazakhs. 4) The nine united genotypes composed by T663A and G3091A polymorphisms might not be associated with EH in Xinjiang Kazakhs. But the united genotypes composed by T663A GG and T3593C TT might be associated with the lower level of the serum Na~+in Xinjiang Kazakhs. 5) There were more than ten kinds of haplotypes constituted by G2139A, G3091A, T663A and T3593C. The H1 haplotype composed by the alleles with 2139G, 3091A, 663G and 3593T might be associated with EH in Xinjiang Kazakhs, however, the H2 haplotype composed by the alleles with 2139A, 3091A, 663A and 3593C might decreased the risk of EH in Xinjiang Kazakhs. 6) The salt sensitive gene --- ENaC gene are still one of the important candidate genes related to EH in Xinjiang Kazakhs.
引文
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