CYP2C19 Loss-of-Function Is an Independent Risk Factor of Coronary Artery Disease in Patients With Hypertension.

Objective: Cytochrome P450 2C19 (CYP2C19) is affected by its gene polymorphisms and is involved in the occurrence and development of diseases. To assess the relationship between CYP2C19 polymorphisms and coronary artery disease (CAD) susceptibility in hypertensive patients.

Methods: This study retrospectively analyzed 3404 hypertensive patients who were admitted to Meizhou People's Hospital from November 2019 to August 2023, including 1438 CAD patients and 1966 nonCAD individuals. The CYP2C19 rs4244285 (681G>A, *2) and rs4986893 (636G>A, *3) polymorphisms were genotyped by polymerase chain reaction (PCR)-chip technique. The relationship between CYP2C19 polymorphisms and CAD was analyzed.

Results: There were 1567 (46.0%), 1491 (43.8%), and 346 (10.2%) individuals with CYP2C19 extensive metabolizer (EM) (CYP2C19*1/*1), intermediate metabolizer (IM) (CYP2C19*1/*2 and *1/*3), and poor metabolizer (PM) (CYP2C19*2/*2, *2/*3, and *3/*3) phenotype. The CAD patients had higher frequencies of the *2 allele (30.2% vs. 26.0%, p < 0.001), *3 allele (4.9% vs. 3.8%, p = 0.021) and lower frequency of *1 allele (64.8% vs. 70.2%, p < 0.001) than controls. Logistic regression analysis showed that body mass index (BMI) ≥ 24.0 kg/m² (odds ratio (OR): 1.364, 95% confidence interval (CI): 1.184-1.571, p < 0.001), history of alcoholism (OR: 1.761 95% CI: 1.211-2.559, p = 0.003), and CYP2C19 IM + PM phenotypes (IM + PM vs. EM, OR: 1.314, 95% CI: 1.145-1.508, p < 0.001) were independent risk factors for CAD in hypertensive patients.

Conclusions: CYP2C19 loss-of-function, BMI ≥ 24.0 kg/m², and history of alcoholism were independent risk factors for CAD in hypertensive patients. Hypertensive patients who carried CYP2C19 loss-of-function need to be aware of the risk of developing CAD, and it provides further evidence for the relationship between CYP2C19 and CAD.