Association of AGTR1 A1166C and CYP2C9∗3 Gene Polymorphisms with the Antihypertensive Effect of Valsartan

Abstract

Background. The differences in the antihypertensive treatment with angiotensin type II receptor blockers (ARBs) may be attributed to polymorphisms in genes involving drug-targeted receptor and drug metabolism. The present study aimed to investigate whether the antihypertensive effect of the ARB drug valsartan was associated with angiotensin II type 1 receptor (AGTR1) gene polymorphism (A1166 C) and cytochrome P450 enzyme 2C9 (CYP2C9) gene polymorphism (CYP2C9∗3). Methods. 281 patients with hypertension who received valsartan monotherapy in the past month were included in this retrospective study. Polymerase chain reaction-melting curve analysis was performed to genotype the AGTR1 and CYP2C9 gene polymorphisms. Based on the systolic blood pressure (SBP) and diastolic blood pressure (DBP) at the time of visit, the patients were divided into well-controlled group (n = 144, SBP/DBP <140/90 mmHg) and poorly controlled group (n = 137, SBP/DBP ≥140/90 mmHg). Results. Older age, decreased history of drinking, a higher proportion of mild-to-moderate hypertension, lower alanine aminotransferase levels, and higher high-density lipoprotein cholesterol levels were observed in the well-controlled group than the poorly controlled group. Higher frequencies of the C allele and AC + CC genotype of AGTR1 A1166C were detected in the well-controlled than the poorly controlled patients ( $P$  = 0.005 and $P$  = 0.006). After adjustment for demographic and environmental factors, the CC + AC genotype of AGTR1 A1166C was markedly linked to better hypertension control with valsartan treatment compared to the AA genotype (odds ratio: 2.836, 95% confidence interval: 1.199–6.705, $P$  = 0.018). No significant difference was observed in the allele or genotype distribution of CYP2C9∗3 polymorphism between well-controlled and poorly controlled patients. Conclusions. The current data suggested that the AGTR1 A1166 C polymorphism may be associated with the antihypertensive effect of valsartan, and carriers with AC and CC genotypes may have a better antihypertensive efficacy response to valsartan treatment.