Association between human atrial natriuretic peptide Val7Met polymorphism and baseline blood pressure, plasma trough irbesartan concentrations, and the antihypertensive efficacy of irbesartan in Rural Chinese patients with essential hypertension

Abstract

Background: Individual variations in the pharmacokineticsand pharmacodynamics of antihypertensive drugs are influenced by genetic and environmental factors. The ANP gene, which encodes the precursor of atrial natriuretic peptide (ANP), is among the candidate genes for genetic susceptibility to hypertension. Objective: This study examined the relationshipbetween ANP Val7Met polymorphism (Single Nucleotide Polymorphism database ID: rs5063) and baseline blood pressure (BP), plasma trough irbesartan concentrations, and the antihypertensive efficacy of irbesartan in rural Chinese patients with essential hypertension. Methods: Patients with essential hypertension whohad taken no antihypertensive medications within 4 weeks of study initiation received oral irbesartan 150 mg/d for 4 weeks. Genotyping was performed for all patients. BP was measured before dosing on the 1st and 28th days of treatment. Plasma irbesartan concentrations were measured using high-performance liquid chromatography with fluorescent detection. Antihypertensive efficacy was defined as attainment of a diastolic BP (DBP) <90 mm Hg (DBP analysis), a systolic BP (SBP) <140 mm Hg (SBP analysis), and a DBP <90 mm Hg and SBP <140 mm Hg (DBP and SBP analysis). Results: The study included 756 patients, 621 with the Val/Val genotype and 135 with the Val/Met+Met/Met genotypes. There were no significant differences in age, body mass index, sex, education level, occupation, alcohol consumption, or smoking status between the 2 groups. Patients with the Val/Met+Met/Met genotypes had a significantly lower mean baseline DBP compared with those with the Val/Val genotype (adjusted regression coefficient [SE]: −2.5 [1.0] mm Hg; P = 0.012) and significantly lower mean steady-state plasma trough irbesartan concentrations (adjusted regression coefficient: −12.6 [4.1]; P = 0.002). No significant association was found between antihypertensive efficacy and Val7Met polymorphism in the overall population, but in an analysis by baseline DBP status, patients with the Val/Met+Met/Met genotype a baseline DBP ≥100 mm Hg had significantly smaller reductions in DBP (adjusted regression coefficient: −5.7 [1.4] mm Hg; P < 0.001) and SBP compared with those with the Val/Val genotype and a baseline DBP ≥100 mm Hg (adjusted regression coefficient: −9.8 [2.9] mm Hg; P < 0.001). Conclusion: The findings of this study suggest thatin these rural Chinese patients with essential hypertension, ANP Val7Met polymorphism may be a genetic marker for baseline DBP, plasma irbesartan concentrations, and the antihypertensive efficacy of short-term irbesartan therapy.