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.

Association of maternal phthalates exposure and metabolic gene polymorphisms with congenital heart diseases: a multicenter case-control study

“…It has been reported that rs1057910 genotype of CYP2C9 was related to increased risk of adenoma recurrence (aRR = 1.47, 95% CI: 1.19–1.83) [ 39 ], or developing sporadic colorectal carcinoma (aOR = 2.77, 95% CI: 1.1653–4.643) [ 40 ]. In addition, for the two common polymorphic loci rs12248560 and rs4244285 of CYP2C19 , the genotype of rs12248560 was associated with decreased breast cancer risk (aOR = 0.77, 95% CI: 0.65–0.93) [ 41 ], while rs4244285 polymorphism was related to higher risk of epilepsy (aOR = 4.24, 95% CI: 2.52–7.15) [ 42 ], long-term ischemic stroke events (hazard ratio: 1.64, 95% CI: 1.06–2.53) [ 43 ], hypertension (aOR = 2.433, 95% CI: 1.797–3.293) [ 44 ]. Meanwhile, several studies have observed that CYP2C9 rs1057910 polymorphism was associated with increased risk for adenoma recurrence (aRR = 1.47, 95% CI 1.19–1.83) [ 39 ], or developing sporadic colorectal carcinoma (aOR = 2.589, 95% CI: 1.549–4.330) [ 40 ].…”

“…Genomic DNA was extracted with magnetic bead method (BioTeke, Wuxi, China) according to the recommended protocol. Twenty SNPs in the UGT1A7 , UGT2B7 , UGT2B15 , CYP2C19 , CYP2C9 were selected based on the following principal criteria: (1) an association with diseases in previous studies or the metabolic level of phthalates [ 28 – 44 ], (2) a minor allele frequency > 0.05 in Han Chinese. In total, 20 SNPs were selected.…”

Differential Expression of Serum Proinflammatory Cytokine TNF-α and Genetic Determinants of TNF-α, CYP2C19*17, miR-423 Genes and Their Effect on Coronary Artery Disease Predisposition and Progression

“…This CYP2C family member catalyzes the metabolism of the arachidonic acid to endothelium-derived hyperpolarizing factor (EDHF), which causes blood vessel relaxation, including the coronary arteries [44]. The defective production of EDHF (due to CYP2C19 gene variants) can cause renal dysfunction and CVD [44]. In addition, the reactions catalyzed by CYP2C generate ROS in coronary arteries [44].…”

CYP2C19 *2/*2 Genotype is a Risk Factor for Multi-Site Arteriosclerosis: A Hospital-Based Cohort Study

“…CYP2C19 variants were detected by CYP2C19 genotyping kit (BaiO Technology Co., Ltd, Shanghai, China) with PCR-gene chip method. 37 The specific detection steps are carried out by referring to the method published by our colleagues before. 37…”

“…37 The specific detection steps are carried out by referring to the method published by our colleagues before. 37…”