Key result
AGTR1 AC/CC genotypes in males linked to ~3 mm Hg greater systolic reduction with irbesartan.
Why the study?
It was unknown whether CYP2C9*3 and AGTR1 (1166A>C) gene polymorphisms are associated with the risk of essential hypertension and the antihypertensive effect of irbesartan.
Do CYP2C9*3 and AGTR1 (1166A>C) gene polymorphisms influence the risk of essential hypertension and the antihypertensive effect of irbesartan?
Observational (n=2,343)
Do CYP2C9*3 and AGTR1 (1166A>C) gene polymorphisms influence the risk of essential hypertension and the antihypertensive effect of irbesartan?
Polymorphisms in CYP2C9*3 and AGTR1 (1166A>C) are associated with the magnitude of blood pressure reduction in response to irbesartan, suggesting a pharmacogenetic influence on its efficacy.
Answers are grounded in this paper and cite their sources.
Hypothesis-generating for AGTR1-guided irbesartan dosing in men; leaves open clinical utility pending randomized trials.
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.
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Dong et al. (2021) conducted an observational in Essential hypertension (n=2,343). Irbesartan vs. Different genotypes (CYP2C9*3 *1*1 and AGTR1 AA) was evaluated on Blood pressure reduction (p=< 0.05). Male subjects with AGTR1 AC/CC genotypes had larger systolic (32.3 vs 29.3 mm Hg) and diastolic (21.6 vs 19.4 mm Hg) blood pressure reductions with irbesartan compared to the AA genotype (P<0.05).
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