CYP2C19 loss-of-function is associated with increased risk of hypertension in a Hakka population: a case-control study

Abstract

AbstractBackgroundGenetic factors have a certain proportion in the risk factors of hypertension. The purpose was to investigate the relationship of cytochrome P450 2C19 (CYP2C19) polymorphisms with hypertension in Hakka population.MethodsThe study included 1,872 hypertensive patients and 1,110 controls. The genotypes ofCYP2C19rs4244285 and rs4986893 of all individuals were detected and analyzed.ResultsThe genotype and allele distributions ofCYP2C19rs4244285 were significantly different between hypertension group and control group. TheCYP2C19*1/*1 genotype was the most predominant among the subjects (40.8%), followed by theCYP2C19*1/*2 genotype (40.5%). The percentage ofCYP2C19*1, *2, and *3 allele was 64.2%, 30.8%, and 5.0%, respectively. The proportion of intermediate metabolizers (IM) (49.3% vs. 42.9%), poor metabolizers (PM) (14.3% vs. 8.9%) (P < 0.001), andCYP2C19*2 allele (33.8% vs. 25.7%,P < 0.001) in hypertension group was significantly higher than that in control group. Multivariate logistic regression (adjusted for gender, age, smoking, and drinking) indicated thatCYP2C19*1/*2, *1/*3, and *2/*2 genotypes may increase susceptibility to hypertension. And theCYP2C19IM genotype (IM vs. EM: OR 1.514, 95% CI: 1.291–1.775,P < 0.001), PM genotype (PM vs. EM: OR 2.120, 95% CI: 1.638–2.743,P < 0.001), IM + PM genotypes (IM + PM vs. EM: OR 1.617, 95% CI: 1.390–1.882,P < 0.001) may increase risk of hypertension.ConclusionsCYP2C19loss-of-function (IM, PM genotypes) is independent risk factor for hypertension susceptibility. Specifically, the risk genotypes includeCYP2C19*1/*2, *1/*3, and *2/*2.