Association analysis between hypertension and CYBA, CLCNKB, and KCNMB1 functional polymorphisms in the Japanese population -: The Suita study
Association analysis between hypertension and CYBA, CLCNKB, and KCNMB1 functional polymorphisms in the Japanese population -: The Suita study
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DOI：
10.1253/circj.69.138
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发表时间：
2005-02-01
影响因子：
3.3
通讯作者：
Tomoike, H
中科院分区：
文献类型：
--
作者：
Kokubo, Y;Iwai, N;Tomoike, H
背景：结果的可重复性对遗传关联研究的有效性至关重要。最近，3个功能多态性，CYBA中的G(-930)A， CLCNKB中的T481S和KCNMBI中的E65K，被报道与血压（BP）状态相关，本研究的目的是通过代表日本普通人群的大型队列来证实这些发现。方法和结果研究人群包括从Suita研究中招募的3,652名受试者，作为日本普通人群的代表。采用TaqMan法测定3个多态性的基因型。Logistic分析显示，CYBA/G(-930)A多态性与男性高血压相关。在男性人群中，GG基因型与GA+AA基因型的比值比为1.27（95%可信区间1.01 ~ 1.57,p=0.034）。此外，GG基因型受试者的收缩压和舒张压值残差显著高于GA或AA基因型受试者（p=0.0007）。然而，基因型对BP状态的显著影响未在女性人群中观察到。CLCNKB/T481S和KCNMB1/E65K多态性的意义在本研究中没有得到证实。结论本研究证实了CYBA基因G(-930)A多态性的意义，具有足够的统计学意义，加强了该多态性在高血压发病机制中起重要作用并具有易感性的假设。
Background Reproducibility of results is important for the validity of genetic association studies. Recently, 3 functional polymorphisms, G(-930)A in CYBA, T481S in CLCNKB, and E65K in KCNMBI, were reported to be associated with blood pressure (BP) status and the aim of this study was to confirm those findings using a large cohort representing the general Japanese population.Methods and Results The study population consisted of 3,652 subjects recruited from the Suita study as representive of the general population in Japan. The genotypes of the 3 polymorphisms were determined by the TaqMan method. Logistic analysis indicated that the CYBA/G(-930)A polymorphism was associated with hypertension in male subjects. In the male population, the odds ratio of the GG genotype over GA+AA was 1.27 (95% confidence interval 1.01-1.57, p=0.034). Moreover, residuals of systolic and diastolic BP values were significantly higher in subjects with the GG genotype than in those with the GA or AA genotype (p=0.0007). However, such significant effects of the genotype on BP status were not observed in the female population. The significance of the CLCNKB/T481S and KCNMB1/E65K polymorphisms were not replicated in the present study.Conclusion The significance of the G(-930)A polymorphism of CYBA was confirmed in the present study with adequate statistical power, which strengthens the hypothesis that this polymorphism is important in the pathogenesis of hypertension and confers susceptibility.