The Association of ADRB1 and CYP2D6 Polymorphisms With Antihypertensive Effects and Analysis of Their Contribution to Hypertension Risk

Abstract

Background: Genetic factors have a vital influence on the pathogenesis of hypertension. In this retrospective study, we aimed to evaluate the association of ADRB1 and CYP2D6 polymorphisms with antihypertensive effects and perform an analysis of their contribution to hypertension risk.

Methods: A total of 261 healthy individuals and 261 essential hypertension patients treated with metoprolol for 12 weeks were enrolled. ADRB1 and CYP2D6 genotypes were identified by xTAG liquid chip technology. We used multivariate logistic regression and a generalized linear mixed model to assess hypertension-related risk factors.

Results: The allele frequencies of ADRB1 and CYP2D6 variants were 59.8% and 64.6% in the essential hypertension group and 70.3% and 65.9% in the controls, respectively. The genotype and allele distribution of ADRB1 were significantly different between the 2 groups (P < 0.05), but there was no significant difference in CYP2D6 distribution (P = 0.91 and 0.88). By logistic regression analysis, high fasting plasma glucose, smoking, high triglyceride and the Gly/Gly polymorphism in Arg389Gly ADRB1 all emerged as independent risk factors for hypertension. Additionally, the ADRB1 genotype played a major role in the antihypertensive effect of metoprolol and the patients with the Gly389Gly genotype showed a significantly better response to metoprolol than did those with a heterozygous ADRB1 mutation (Arg389Gly) (P = 0.027).

Conclusions: The results demonstrate that Gly/Gly polymorphism in Arg389Gly ADRB1 was an independent risk factor together with high fasting plasma glucose, smoking and high triglyceride; moreover, the patients who carried the Gly389Gly genotype had a significantly improved metoprolol antihypertensive effect than those with ADRB1.

Keywords: Cytochrome P450 2D6; Essential hypertension; Metoprolol; Risk factor; β1-adrenergic receptor.