Association of Cytochrome P450 2C9*3 and Angiotensin II Receptor 1 (1166A>C) Gene Polymorphisms With the Antihypertensive Effect of Irbesartan.

Background: To analyze whether the cytochrome P450 enzyme 2C9*3 (CYP2C9*3) and angiotensin II receptor 1 (AGTR1) (1166A>C) gene polymorphisms are associated with the risk of essential hypertension (EH) and the antihypertensive effect of irbesartan.

Methods: A total of 2,057 EH patients and 286 healthy controls were enrolled for genotyping in which 598 EH patients were given irbesartan 150 mg/day for 4 weeks. Blood pressure of all subjects were determined before and at the end of 4-week treatment.

Results: There was no significant difference in genotype frequencies of CYP2C9*3 and AGTR1 (1166A>C) between EH and control groups. Subjects with *1*3/*3*3 genotypes of the CYP2C9*3 gene had larger systolic and diastolic blood pressure reductions (34.9 ± 15.5 vs. 29.3 ± 10.2 mm Hg and 22.8 ± 9.0 vs. 19.6 ± 8.5 mm Hg, respectively) compared with the *1*1 genotype. For AGTR1 (1166A>C) polymorphisms, although there was no significant difference among AC, CC, and AA genotypes, male subjects with AC/CC genotypes had larger systolic and diastolic blood pressure reductions (32.3 ± 1.3 vs. 29.3 ± 0.5 mm Hg and 21.6 ± 0.8 vs. 19.4 ± 0.1 mm Hg, respectively, P < 0.05) in response to irbesartan treatment compared with the AA genotype.

Conclusions: Polymorphisms of CYP2C9*3 and AGTR1 (1166A>C) are not significantly different between EH and healthy controls. Male subjects with AC and CC genotypes of AGTR1 (1166A>C) show better antihypertensive effect of irbesartan than the AA genotype.