Yamada Yoshiji, Ando Fujiko, Shimokata Hiroshi
Department of Human Functional Genomics, Life Science Research Center, Mie University, Tsu, Mie, Japan.
Hypertens Res. 2009 May;32(5):325-31. doi: 10.1038/hr.2009.23. Epub 2009 Mar 13.
Although various loci and genes have been implicated in predisposition to hypertension by genetic linkage analyses and candidate gene association studies, the genes that confer susceptibility to this condition remain to be identified definitively. We have now examined the relationships of 22 candidate gene polymorphisms with the prevalence of hypertension and with blood pressure (BP) in a 6-year population-based longitudinal cohort study and observed significant relationships of three polymorphisms of SORBS1, GCK and WISP1 with hypertension. The 2233 subjects (1106 women, 1127 men) were aged 40-79 years and were randomly recruited to a population-based prospective cohort study of aging and age-related diseases in Japan. BP was measured with subjects having rested in the sitting position for at least 15 min. Genotypes for the 682A --> G (Thr228Ala) polymorphism of SORBS1, the -30G --> A polymorphism of GCK and the 2364A --> G polymorphism of WISP1 were determined by melting curve analysis. Longitudinal analysis with a generalized estimating equation revealed that the polymorphisms of SORBS1 and GCK and that of WISP1 were significantly associated with the prevalence of hypertension in women and men, respectively. Longitudinal analysis with a mixed-effect model revealed that the polymorphism of SORBS1 was significantly related to diastolic BP in women and that those of GCK and WISP1 were significantly related to both systolic and diastolic BP in women and men, respectively. These results suggest that SORBS1 and GCK are susceptibility loci for hypertension in Japanese women and that WISP1 is such a locus in men.
尽管通过基因连锁分析和候选基因关联研究发现了各种基因座和基因与高血压易感性有关，但导致这种疾病易感性的基因仍有待明确鉴定。在一项基于人群的6年纵向队列研究中，我们现已检测了22种候选基因多态性与高血压患病率及血压（BP）之间的关系，并观察到SORBS1、GCK和WISP1的三种多态性与高血压之间存在显著关系。这2233名受试者（1106名女性，1127名男性）年龄在40 - 79岁之间，是从日本一项基于人群的衰老和年龄相关疾病前瞻性队列研究中随机招募的。在受试者至少静坐休息15分钟后测量血压。通过熔解曲线分析确定SORBS1的682A→G（Thr228Ala）多态性、GCK的 - 30G→A多态性和WISP1的2364A→G多态性的基因型。采用广义估计方程进行纵向分析表明，SORBS1和GCK的多态性以及WISP1的多态性分别与女性和男性的高血压患病率显著相关。采用混合效应模型进行纵向分析表明，SORBS1的多态性与女性的舒张压显著相关，而GCK和WISP1的多态性分别与女性和男性的收缩压和舒张压显著相关。这些结果表明，SORBS1和GCK是日本女性高血压的易感基因座，而WISP1是男性的易感基因座。
