Associations between antihypertensive drug-related gene polymorphisms and cardiovascular outcomes in hypertensive patients: a gene-drug interaction study

Antihypertensive therapy is pivotal in preventing cardiovascular events, yet treatment efficacy varies significantly among individuals due to genetic polymorphisms.This study aimed to investigate the association between specific antihypertensive drug-related gene polymorphisms, the use of corresponding sensitive drugs, and the risks of stroke and coronary heart disease (CHD) in a community-based hypertensive population. A cross-sectional study was conducted among 29,662 hypertensive patients from primary care centers in Changsha County, China. Seven gene loci (ACE(I/D), CYP2C9*3,AGTR1(1166 A > C), CYP2D6*10,ADRB1(1165G > C), CYP3A5*3, and NPPA(2238T > C))were genotyped.Patients were stratified into sensitive or non-sensitive genotype groups. Logistic regression and interaction analysis were employed to assess gene-drug interactions on cardiovascular outcomes. The prevalence of stroke and CHD was 2.8% and 19.5%, respectively. Carriers of sensitive genotypes for AGTR1, CYP2D6*10, and ADRB1 taking sensitive drugs exhibited a significantly lower risk of stroke (ORs: 0.39, 0.67, 0.68; all P < 0.01). Similarly, sensitive genotype carriers for CYP2D6*10, CYP3A5*3, and NPPA taking sensitive drugs had a reduced risk of CHD (ORs: 0.92, 0.88, 0.53; all P < 0.05). A significant additive interaction was identified between AGTR1(1166 A > C) and sensitive drug use on CHD risk (AP = 0.08). Pharmacogenomics-guided antihypertensive therapy is associated with a reduced risk of stroke and CHD in hypertensive patients. The interaction between AGTR1(1166 A > C) genotype and drug use underscores the potential of personalized medicine in optimizing cardiovascular disease prevention strategies in primary care.