Yamada Yoshiji, Ando Fujiko, Shimokata Hiroshi
Department of Human Functional Genomics, Life Science Research Center, Mie University, Mie 514-8507, Japan.
Int J Mol Med. 2007 Apr;19(4):675-83.
Hypertension is a complex multifactorial disorder that is thought to result from an interaction between genetic background and environmental factors. 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 examined the relations of nine candidate gene polymorphisms to blood pressure (BP) and the prevalence of hypertension in a population-based study. The 2238 subjects (1110 women, 1128 men) were aged 40 to 79 years and were randomly recruited for a population-based prospective cohort study of aging and age-related diseases in Japan. BP was measured with subjects having rested in a sitting position for at least 15 min. Genotypes for the 160C-->T (Arg54Trp) polymorphism of QPCT, the C-->T (Pro198Leu) polymorphism of GPX1, the 137,346T-->C polymorphism of FYN, the -344C-->T polymorphism of CYP11B2, and the A-->G (Ser49Gly) polymorphism of ADRB1 were determined with a fluorescence-based allele-specific DNA primer assay system; those for the A-->G polymorphism of CNR2, the I/D (22,375delAC) polymorphism of CAV1, and the -1213T-->C polymorphism of ESR2 by melting curve analysis, and that for the (GT)n polymorphism of COL1A2 were determined by DNA fragment analysis. The polymorphism of FYN was associated with systolic and diastolic BP in women. In men, polymorphisms of CNR2, QPCT, GPX1, COL1A2, CYP11B2, and ESR2 were associated with systolic and diastolic BP, those of CAV1 and FYN with systolic BP, and that of ADRB1 with diastolic BP. The polymorphisms of QPCT and CYP11B2 were also associated with the prevalence of hypertension in men. These results suggest that polymorphisms of QPCT and CYP11B2 are determinants of BP and the development of hypertension in Japanese men.
高血压是一种复杂的多因素疾病,被认为是遗传背景和环境因素相互作用的结果。尽管通过遗传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,但确切导致这种疾病易感性的基因仍有待确定。我们在一项基于人群的研究中,研究了9种候选基因多态性与血压(BP)及高血压患病率的关系。这2238名受试者(1110名女性,1128名男性)年龄在40至79岁之间,是从日本一项基于人群的衰老及与年龄相关疾病的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。使用基于荧光的等位基因特异性DNA引物检测系统确定QPCT基因160C→T(Arg54Trp)多态性、GPX1基因C→T(Pro198Leu)多态性、FYN基因137346T→C多态性、CYP11B2基因 - 344C→T多态性以及ADRB1基因A→G(Ser49Gly)多态性的基因型;通过熔解曲线分析确定CNR2基因A→G多态性、CAV1基因I/D(22375delAC)多态性以及ESR2基因 - 1213T→C多态性的基因型,通过DNA片段分析确定COL1A2基因(GT)n多态性的基因型。FYN基因多态性与女性的收缩压和舒张压相关。在男性中,CNR2、QPCT、GPX1、COL1A2、CYP11B2和ESR2基因多态性与收缩压和舒张压相关,CAV1和FYN基因多态性与收缩压相关,ADRB1基因多态性与舒张压相关。QPCT和CYP11B2基因多态性也与男性高血压患病率相关。这些结果表明,QPCT和CYP11B2基因多态性是日本男性血压及高血压发生的决定因素。