Yamada Yoshiji, Kato Kimihiko, Yoshida Tetsuro, Yokoi Kiyoshi, Matsuo Hitoshi, Watanabe Sachiro, Ichihara Sahoko, Metoki Norifumi, Yoshida Hidemi, Satoh Kei, Aoyagi Yukitoshi, Yasunaga Akitomo, Park Hyuntae, Tanaka Masashi, Nozawa Yoshinori
Department of Human Functional Genomics, Life Science Research Center, Mie University, Mie 514-8507, Japan.
Int J Mol Med. 2008 Jan;21(1):83-9.
Although various environmental factors, such as a high-salt diet, a smoking habit, excessive alcohol intake, and physical inactivity, influence the development of hypertension, genetic variation also contributes to an individual's susceptibility to this condition. The purpose of the present study was to identify gene polymorphisms that confer susceptibility or resistance to hypertension, and thereby contribute to the prediction of the genetic risk for this condition. The study population comprised 2752 unrelated Japanese individuals (1370 men, 1382 women), including 1276 subjects with hypertension (774 men, 502 women) and 1476 controls (596 men, 880 women). The genotypes for 50 polymorphisms of 35 candidate genes were determined by a method that combines polymerase chain reaction and sequence-specific oligonucleotide probes with suspension array technology. Evaluation of genotype distributions by the Chi-square test and subsequent multivariable logistic regression analysis with adjustment for age, sex, body mass index, smoking status, and the prevalence of diabetes mellitus and hypercholesterolemia revealed that the -14C-->T polymorphism of ABCA1, the C-->G (Ser2229Cys) polymorphism of ROS1, the C-->T (Asn591Asn) polymorphism of LDLR, the 13989A-->G (Ile118Val) polymorphism of CYP3A4, the C-->G and A-->C polymorphisms of ADIPOR1, and the -519A-->G polymorphism of MMP1 were significantly (P<0.05) associated with the prevalence of hypertension. Systolic and diastolic blood pressure differed significantly among genotypes for the -14C-->T polymorphism of ABCA1 and the C-->G (Ser2229Cys) polymorphism of ROS1, with the variant T and G alleles, respectively, being related to increased blood pressure. These results suggest that polymorphisms of ABCA1 and ROS1 are determinants of blood pressure and the development of hypertension in Japanese individuals. Determination of genotypes for ABCA1 and ROS1 may thus prove informative for the prediction of the genetic risk for hypertension.
尽管各种环境因素，如高盐饮食、吸烟习惯、过量饮酒和缺乏身体活动，都会影响高血压的发生发展，但基因变异也会影响个体对这种疾病的易感性。本研究的目的是确定赋予高血压易感性或抗性的基因多态性，从而有助于预测这种疾病的遗传风险。研究人群包括2752名无亲缘关系的日本个体（1370名男性，1382名女性），其中包括1276名高血压患者（774名男性，502名女性）和1476名对照者（596名男性，880名女性）。通过将聚合酶链反应和序列特异性寡核苷酸探针与悬浮阵列技术相结合的方法，确定了35个候选基因的50个多态性的基因型。通过卡方检验评估基因型分布，并随后进行多变量logistic回归分析，对年龄、性别、体重指数、吸烟状况以及糖尿病和高胆固醇血症的患病率进行调整，结果显示，ABCA1基因的-14C→T多态性、ROS1基因的C→G（Ser2229Cys）多态性、LDLR基因的C→T（Asn591Asn）多态性、CYP3A4基因的13989A→G（Ile118Val）多态性、ADIPOR1基因的C→G和A→C多态性以及MMP1基因的-519A→G多态性与高血压患病率显著相关（P<0.05）。ABCA1基因的-14C→T多态性和ROS1基因的C→G（Ser2229Cys）多态性的基因型之间，收缩压和舒张压存在显著差异，变异的T和G等位基因分别与血压升高有关。这些结果表明，ABCA1和ROS1基因的多态性是日本个体血压和高血压发生发展的决定因素。因此，确定ABCA1和ROS1基因的基因型可能对预测高血压的遗传风险具有参考价值。
