Association of (pro)renin receptor gene polymorphisms with lacunar infarction and left ventricular hypertrophy in Japanese women: The Ohasama study

Recent studies have revealed that (pro)renin receptor ((P)RR), a newly identified member of the renin-angiotensin system, is associated with organ damage that occurs with cardiovascular disease. We investigated the association of genetic polymorphisms in the (P)RR gene with lacunar infarction, white matter hyperintensity and left ventricular hypertrophy (LVH) in a Japanese general population recruited from the Ohasama study, a Japanese cohort study. A total of 779 subjects (men250 and women529) were recruited. For the association study, we selected three polymorphisms: 782AG (rs2968915), intervening sequence (IVS)5169CT (rs5918007) and 1513AG (rs6609080). In women, the prevalence of lacunar infarction and LVH was significantly higher in subjects with the 1513GG genotype than in those with the AA or AG genotypes (lacunar infarction: P0.01, LVH: P0.003). Plasma renin activity (PRA) levels in women with the GG genotype were significantly lower than in women with the AA or AG genotypes (P0.01). Multiple logistic regression analysis adjusted for confounding factors demonstrated that 1513AG polymorphism was significantly and independently associated with the risk of lacunar infarction (trend P0.03) and LVH (trend P0.003). In men, there were no significant differences in lacunar infarction, LVH or PRA levels among the three genotypes. The polymorphism of the (P)RR gene 1513AG is associated with lacunar infarction and LVH in Japanese women. These results suggest that (P)RR has a role in organ damage in humans.