Matsubara Mitsunobu, Sato Tomomi, Nishimura Takuya, Suzuki Michiko, Kikuya Masahiro, Metoki Hirohito, Michimata Mari, Tsuji Ichiro, Ogihara Toshio, Imai Yutaka
Division of Molecular Medicine and Gene Transfer Research, Center for Translational and Advanced Animal Research on Human Diseases, Tohoku University School of Medicine, Sendai, Japan.
Hypertens Res. 2004 Jan;27(1):1-6. doi: 10.1291/hypres.27.1.
Genetic polymorphisms of the aldosterone synthase gene (CYP11B2) have been major targets of studies into the genetic factors involved in hypertension. We have identified three genetic variants of CYP11B2, -344C/T at the promoter region, a conversion in intron 2 from the CYP11B2 sequence to the CYP11B1 sequence, and R173K in exon 3, in the Japanese population. -344C/T and R173K were in complete linkage disequilibrium in CYP11B2, and -344C/T was in strong, but not complete, linkage disequilibrium with the polymorphism in intron 2. Thus, two genetic polymorphisms, -344C/T and the gene conversion in intron 2, were investigated in association with home blood pressure (BP) values and clinical parameters in 1,242 subjects aged 40 and over in Ohasama, a rural Japanese community. Hypertension was defined as being treated with antihypertensive medication and/or having home BP values of more than 135 mmHg in systole and/or 85 mmHg in diastole. The results demonstrated that the -344T allele was significantly associated with increased prevalence of hypertension (p=0.015 in multiple logistic regression analysis, adjusted by age, gender, BMI, and smoking status), though BP level was unaltered. This allele was also significantly related to the prevalence of cardiovascular diseases in the older population (60 < or = age, p=0.014). The resting polymorphism, a gene conversion in CYP11B2 intron 2, was not associated with any clinical parameters. Therefore, -344C/T polymorphism in CYP11B2 was considered an independent genetic factor possibly associated with hypertension or atherosclerotic diseases in the Japanese population.
醛固酮合酶基因（CYP11B2）的基因多态性一直是高血压相关遗传因素研究的主要目标。我们在日本人群中鉴定出CYP11B2的三种基因变异，即启动子区域的-344C/T、内含子2中从CYP11B2序列到CYP11B1序列的转换以及外显子3中的R173K。-344C/T和R173K在CYP11B2中处于完全连锁不平衡状态，而-344C/T与内含子2中的多态性处于强但不完全的连锁不平衡状态。因此，我们在日本农村社区大岛的1242名40岁及以上受试者中，研究了两种基因多态性，即-344C/T和内含子2中的基因转换与家庭血压（BP）值及临床参数的关系。高血压的定义为正在接受抗高血压药物治疗和/或家庭收缩压值超过135 mmHg和/或舒张压值超过85 mmHg。结果表明，-344T等位基因与高血压患病率增加显著相关（多因素逻辑回归分析中p = 0.015，经年龄、性别、BMI和吸烟状况校正），尽管血压水平未改变。该等位基因也与老年人群（年龄≥60岁）心血管疾病的患病率显著相关（p = 0.014）。静息多态性，即CYP11B2内含子2中的基因转换，与任何临床参数均无关联。因此，CYP11B2中的-344C/T多态性被认为是日本人群中可能与高血压或动脉粥样硬化疾病相关的独立遗传因素。
