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

ABSTRACT

BACKGROUND: Genetic 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. METHODS: The study included 1,872 hypertensive patients and 1,110 controls. The genotypes of CYP2C19 rs4244285 and rs4986893 of all individuals were detected and analyzed. RESULTS: The genotype and allele distributions of CYP2C19 rs4244285 were significantly different between hypertension group and control group. The CYP2C19 *1/*1 genotype was the most predominant among the subjects (40.8%), followed by the CYP2C19 *1/*2 genotype (40.5%). The percentage of CYP2C19*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), and CYP2C19*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 that CYP2C19 *1/*2, *1/*3, and *2/*2 genotypes may increase susceptibility to hypertension. And the CYP2C19 IM 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. CONCLUSIONS: CYP2C19 loss-of-function (IM, PM genotypes) is independent risk factor for hypertension susceptibility. Specifically, the risk genotypes include CYP2C19 *1/*2, *1/*3, and *2/*2.