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.

Genetic and phenotypic frequency distribution of ACE, ADRB1, AGTR1, CYP2C9*3, CYP2D6*10, CYP3A5*3, NPPA and factors associated with hypertension in Chinese Han hypertensive patients

“…The mutation of the gene AGTR1 (1166A > C) encoding the angiotensin type II receptor will affect the sensitivity of the drug to the receptor and enhance the antihypertensive effect. [21,22] Sun et al [21] found that patients with heterozygous AGTR1 (1166A > C) mutation had a higher systolic and diastolic blood pressure decrease than wild-type patients following candesartan administration. Liu et al [22] reported 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.…”

“…The mutation of the gene AGTR1 (1166A > C) encoding the angiotensin type II receptor will affect the sensitivity of the drug to the receptor and enhance the antihypertensive effect. [21,22] Sun et al [21] found that patients with heterozygous Table 4 Allele frequencies of antihypertensive drug-related gene loci in different regions.…”

“…[21,22] Sun et al [21] found that patients with heterozygous AGTR1 (1166A > C) mutation had a higher systolic and diastolic blood pressure decrease than wild-type patients following candesartan administration. Liu et al [22] reported 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. In this study, we showed that the mutation frequency of AGTR1 (1166A > C) was 6.21%, indicating that most hypertensive patients have a normal level of sensitivity to drugs and receptors, and can be treated with drugs of conventional doses.…”

Personalized antihypertensive treatment guided by pharmacogenomics in China

“…A relationship between CYP2C9 polymorphisms and the pharmacokinetics of ARBs have also been observed, although the clinical impact in terms of BP was modest ( 20 ). It has been shown that AGTR1 mediates the function of ARBs by association with G proteins that activate a phosphatidylinositol-calcium second messenger system ( 21 ). Further, ACE is a key enzyme in the enzyme/substrate cascade reaction of RAS, the polymorphism of which has been associated with the activity of ACE ( 3 ).…”

Influence of Angiotensin II Type 1 Receptor Gene Polymorphism on the Effectiveness of Antihypertensive Therapy in Patients with Hypertension Disease who Suffered Myocardial Infarction according to the Results of Long-Term Follow-Up

“…Існують 120 локусів генів, які пов'язані з регуляцією АТ, але вплив факторів зовнішнього середовища поряд із взаємодією алелів у багатьох локусах призводять до численних варіантів експресії генів [6,7]. І хоча European Society of Cardiology and the European Society of Hypertension в останній настанові не рекомендують використовувати генетичне тестування у рутинній клінічній практиці [5], високу актуальність мають роботи, які демонструють особливості перебігу АГ та чутливість до антигіпертензивної терапії з урахуванням поліморфізму генів, що мають вплив на регулювання АТ [8,9,10].…”