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

• Published in: Journal of human hypertension Vol. 32; no. 11; pp. 781 - 788
• Main Authors: Hu, Shengnan, Cheng, Jun, Weinstock, Justin, Fan, Xiu, Venners, Scott A., Hsu, Yi-Hsiang, Suwen Wu, Pan, Faming, Zha, Xiangdong, Sun, Jinlu, Jiang, Shanqun, Xu, Xiping
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01.11.2018; Nature Publishing Group
• Subjects: 692/308/2056; 692/699/75/243; Body mass index; Cardiovascular research; Chemical properties; Demographic aspects; Dosage and administration; Drug therapy; Epidemiology; Essential hypertension; Gender; Gene polymorphism; Genetic aspects; Genetic polymorphisms; Genotype & phenotype; Health Administration; Health risk assessment; High-performance liquid chromatography; Hypertension; Irbesartan; Kininogens; Medicine; Medicine & Public Health; Patient outcomes; Patients; Physiological aspects; Polymorphism; Public Health; Sex factors in disease; Smoking; China
• ISSN: 0950-9240; 1476-5527; 1476-5527
• DOI: 10.1038/s41371-018-0119-1

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.