Genetic Variation in the CYP2D6 Gene Is Associated With a Lower Heart Rate and Blood Pressure in β-Blocker Users

several beta-blockers are metabolized by the polymorphic enzyme cytochrome p450 2D6 (Cyp2D6). CYP2D6*4 is the main polymorphism leading to decreased enzyme activity. The clinical significance of impaired elimination of beta-blockers is controversial, and most studies suffer from inclusion of small numbers of poor metabolizers (PMs) of Cyp2D6. in this study, the association between CYP2D6*4 and blood pressure or heart rate was examined in 1,533 users of beta-blockers in the rotterdam study, a population-based cohort study. in CYP2D6*4/*4 PMs, the adjusted heart rate in metoprolol users was 8.5 beats/min lower compared with *1/*1 extensive metabolizers (EMs) (P < 0.001), leading to an increased risk of bradycardia in PMs (odds ratio = 3.86; 95% confidence interval 1.68-8.86; P = 0.0014). The diastolic blood pressure in PMs was 5.4 mm Hg lower in users of beta-blockers metabolized by Cyp2D6 (P = 0.017) and 4.8 mm Hg lower in metoprolol users (P = 0.045) compared with ems. PMs are at increased risk of bradycardia.