CAJ | 학술논문

目的研究上皮细胞钠通道(ENaC)基因启动子区G2139A、G3091A、第13外显子区T663A及第2内含子区T3593C位点的单核苷酸多态性(SNPs)及其构成的单体型与新疆哈萨克族人原发性高血压(EH)的相关性.方法采用病例-对照研究的方法,选择牧区哈萨克族EH患者(EH组)252例和血压正常者(NT组)254例,采用聚合酶链反应-限制性片断长度多态性的方法,鉴定不同个体上述4个位点的基因型及等位基因的类型,分析4种SNPs基因型及等位基因在该民族人群的分布特征及其在EH与NT组分布频率的差异,分析4个位点连锁不平衡关系,观察4种SNPs组成的单体型与新疆哈萨克族人EH的相关性.结果新疆哈萨克族αENaC基因存在上述4个位点的SNPs,在总体人群中,G2139A位点AA、AG、GG基因型的频率分别为26.2%、52.3%和21.5%,A、G两种等位基因的分布频率分别为52.37%和47.63%;G3091A位点AA、AG、GG基因型的频率分别为19.0%、52.5%和28.5%,A、G两种等位基因的分布频率分别为45.56%和59.44%;T663A位点AA、AG、GG基因型的频率分别为15.6%、49.9%和34.5%,A、G两种等位基因的分布频率分别为40.53%和59.47%;T3593C位点TT、TC、CC基因型的频率分别为88.5%、10.5%和1.0%,T、C两种等位基因的分布频率分别为93.77%和6.23%.4个位点基因型的分布均符合Hardy-weinberg平衡(P＞0.05).4种SNPs基因型及等位基因的分布频率在EH和NT组差异均无显著性(P＞0.05).4个位点间不存在连锁不平衡关系.单体型分析显示由2139G、3091A、663G和3593T等位基因构成的单体型在EH组显著高于NT组(P＜0.01),由2139A、3091A、663A和3593C等位基因构成的单体型在NT组显著高于ET组(P＜0.05).结论虽然αENaC基因G2139A、G3091A、T663A及T3593C SNPs作为单个位点可能不足以引起个体EH的发生或者仅对EH的发生产生极其微效的作用,但其所构成的单体型可能对新疆哈萨克族人EH的发病发挥重要作用,其中2139G、3091A、663G和3593T等位基因构成的单体型可能与该民族EH的发生相关,而2139A、3091A、663A和3593C等位基因构成的单体型可能是该民族EH发生的保护因子,可降低该民族EH的患病风险,ENaC基因是新疆哈萨克族高血压发生的重要易感基因. 目的研究上皮細胞鈉通道(ENaC)基因啟動子區G2139A、G3091A、第13外顯子區T663A及第2內含子區T3593C位點的單覈苷痠多態性(SNPs)及其構成的單體型與新疆哈薩剋族人原髮性高血壓(EH)的相關性.方法採用病例-對照研究的方法,選擇牧區哈薩剋族EH患者(EH組)252例和血壓正常者(NT組)254例,採用聚閤酶鏈反應-限製性片斷長度多態性的方法,鑒定不同箇體上述4箇位點的基因型及等位基因的類型,分析4種SNPs基因型及等位基因在該民族人群的分佈特徵及其在EH與NT組分佈頻率的差異,分析4箇位點連鎖不平衡關繫,觀察4種SNPs組成的單體型與新疆哈薩剋族人EH的相關性.結果新疆哈薩剋族αENaC基因存在上述4箇位點的SNPs,在總體人群中,G2139A位點AA、AG、GG基因型的頻率分彆為26.2%、52.3%和21.5%,A、G兩種等位基因的分佈頻率分彆為52.37%和47.63%;G3091A位點AA、AG、GG基因型的頻率分彆為19.0%、52.5%和28.5%,A、G兩種等位基因的分佈頻率分彆為45.56%和59.44%;T663A位點AA、AG、GG基因型的頻率分彆為15.6%、49.9%和34.5%,A、G兩種等位基因的分佈頻率分彆為40.53%和59.47%;T3593C位點TT、TC、CC基因型的頻率分彆為88.5%、10.5%和1.0%,T、C兩種等位基因的分佈頻率分彆為93.77%和6.23%.4箇位點基因型的分佈均符閤Hardy-weinberg平衡(P＞0.05).4種SNPs基因型及等位基因的分佈頻率在EH和NT組差異均無顯著性(P＞0.05).4箇位點間不存在連鎖不平衡關繫.單體型分析顯示由2139G、3091A、663G和3593T等位基因構成的單體型在EH組顯著高于NT組(P＜0.01),由2139A、3091A、663A和3593C等位基因構成的單體型在NT組顯著高于ET組(P＜0.05).結論雖然αENaC基因G2139A、G3091A、T663A及T3593C SNPs作為單箇位點可能不足以引起箇體EH的髮生或者僅對EH的髮生產生極其微效的作用,但其所構成的單體型可能對新疆哈薩剋族人EH的髮病髮揮重要作用,其中2139G、3091A、663G和3593T等位基因構成的單體型可能與該民族EH的髮生相關,而2139A、3091A、663A和3593C等位基因構成的單體型可能是該民族EH髮生的保護因子,可降低該民族EH的患病風險,ENaC基因是新疆哈薩剋族高血壓髮生的重要易感基因.
목적 연구상피세포납통도(ENaC)기인계동자구G2139A、G3091A、제13외현자구T663A급제2내함자구T3593C위점적단핵감산다태성(SNPs)급기구성적단체형여신강합살극족인원발성고혈압(EH)적상관성.방법 채용병례-대조연구적방법,선택목구합살극족EH환자(EH조)252례화혈압정상자(NT조)254례,채용취합매련반응-한제성편단장도다태성적방법,감정불동개체상술4개위점적기인형급등위기인적류형,분석4충SNPs기인형급등위기인재해민족인군적분포특정급기재EH여NT조분포빈솔적차이,분석4개위점련쇄불평형관계,관찰4충SNPs조성적단체형여신강합살극족인EH적상관성.결과 신강합살극족αENaC기인존재상술4개위점적SNPs,재총체인군중,G2139A위점AA、AG、GG기인형적빈솔분별위26.2%、52.3%화21.5%,A、G량충등위기인적분포빈솔분별위52.37%화47.63%;G3091A위점AA、AG、GG기인형적빈솔분별위19.0%、52.5%화28.5%,A、G량충등위기인적분포빈솔분별위45.56%화59.44%;T663A위점AA、AG、GG기인형적빈솔분별위15.6%、49.9%화34.5%,A、G량충등위기인적분포빈솔분별위40.53%화59.47%;T3593C위점TT、TC、CC기인형적빈솔분별위88.5%、10.5%화1.0%,T、C량충등위기인적분포빈솔분별위93.77%화6.23%.4개위점기인형적분포균부합Hardy-weinberg평형(P＞0.05).4충SNPs기인형급등위기인적분포빈솔재EH화NT조차이균무현저성(P＞0.05).4개위점간불존재련쇄불평형관계.단체형분석현시유2139G、3091A、663G화3593T등위기인구성적단체형재EH조현저고우NT조(P＜0.01),유2139A、3091A、663A화3593C등위기인구성적단체형재NT조현저고우ET조(P＜0.05).결론 수연αENaC기인G2139A、G3091A、T663A급T3593C SNPs작위단개위점가능불족이인기개체EH적발생혹자부대EH적발생산생겁기미효적작용,단기소구성적단체형가능대신강합살극족인EH적발병발휘중요작용,기중2139G、3091A、663G화3593T등위기인구성적단체형가능여해민족EH적발생상관,이2139A、3091A、663A화3593C등위기인구성적단체형가능시해민족EH발생적보호인자,가강저해민족EH적환병풍험,ENaC기인시신강합살극족고혈압발생적중요역감기인.
Objective To explore the relationship between G2139A,G3091A, T663A, and T3593C single nucleotide polymorphisms (SNPs), which are located at the promoter region,13th exon, and 2nd intron of epithelial sodium channel (ENaC) gene, and their haplotypes with essential hypertension (EH) in Kazakhs in Xinjiang. MethodsA case-control study was conducted including 252 EH patients (EH group) and 254 normotensive subjects (NT group) among Kazakhs in Xinjiang. The four genetic polymorphisms were identified by polymerase chain reaction - restriction fragment length polymorphism. The distribution of the genotypes and alleles in all subjects and the different frequences of these four SNPs between EH group and NT group were analyzed. The linkage disequilibrium and haplotypes of these four SNPs were analyzed. ResultsThese four SNPs of αENaC gene existed in Xinjiang Kazakhs. In all subjects, the distribution frequencies of genotypes AA, AG, and GG at G2139A were 26.2%, 52.3%, and 21.5%, respectively, and those of alleles (A, G) were 52.37% and 47.63%. The distribution frequencies of genotypes AA, AG, and GG at G3091A were 19.0%, 52.5%, and 28.5%, respectively, and those of and alleles (A, G) were 45.56% and 59.44%. The distribution frequencies of genotypes AA, AG, and GG at T663A were 15.6%, 49.9%, and 34.5%, respectively, and those of alleles (A, G) were 40.53% and 59.47%. The distribution frequencies of genotypes TT, TC, and CC at T3593C were 88.5%, 10.5%, and 1.0%, respectively, and those of alleles (T, C) were 93.77% and 6.23%. The distribution of genotypes at these four SNPs were all consistent with Hardy-Weinberg equilibrium in this population (P＞0.05). The distribution frequencies of genotypes and alleles about these four genetic polymorphisms were not significantly different between the EH group and NT group (P＞0.05). However, the frequencies of two haplotypes were found to be significantly different between these two groups (P＜0.05). The haplotype frequency which included 2139G, 3091A, 663G, and 3593T alleles was significantly increased in EH group (P＜0.01), while the haplotype frequency which included 2139A, 3091A, 663A, and 3593C alleles was significantly increased in NT group (P＜0.05). ConclusionsThe haplotypes that are composed of G2139A, G3091A, T663A, and T3593C polymorphisms of αENaC gene may play an important role in the development of EH among Kazakhs in Xinjiang. The haplotypes that are composed of 2139G, 3091A, 663G, and 3593T alleles may aggravate the development of EH. The haplotypes that composed of 2139A, 3091A, 663A, and 3593C alleles may decrease the risk of EH among Kazakhs.