Association of gene polymorphisms with blood pressure and the prevalence of hypertension in community-dwelling Japanese individuals

Abstract

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.