A gender-specific association of the polymorphism Ile197Met in the kininogen 1 gene with plasma irbesartan concentrations in Chinese patients with essential hypertension

This study was conducted to explore interactions in the association of the kininogen (KNG1) Ile197Met polymorphism and gender with plasma concentrations of irbesartan in Chinese patients with essential hypertension. A total of 1100 subjects with essential hypertension received a daily oral dose of 150 mg irbesartan for twenty-eight consecutive days. High-performance liquid chromatography-fluorescence (HPLC) was used to detect plasma irbesartan concentrations on day 28. The KNG1 Ile197Met gene polymorphism was determined using high-throughput TaqMan technology. The frequency distribution of KNG1 Ile197Met genotype conformed to the Hardy-Weinberg equilibrium. After 28 days of treatment, patients with the GG genotype had significantly lower irbesartan concentrations ( P = 0.033) compared to homozygous TT genotype carriers. After stratifying by gender, male G allele carriers had significantly lower irbesartan concentrations (GG, P = 0.015; TG, P = 0.015, respectively) relative to TT genotype after adjusting for age, region, body mass index (BMI), smoking, and alcohol consumption. However, there was no significant difference in female subjects. A further test for a multiplicative interaction between the KNG1 Ile197Met polymorphism and gender in association with ln-plasma irbesartan concentrations in a multiple linear regression model was also significant ( P for interaction = 0.033). This is the first study to suggest that gender may influence the association of the Ile197Met variant of KNG1 with ln-plasma irbesartan concentration. This finding may indicate that the interaction of gender and the KNG1 Ile197Met gene polymorphism can influence plasma trough irbesartan concentrations, which may contribute to a better development of personalized hypertensive treatment in Chinese patients.