Genetic variation in the CYP2D6 gene is associated with a lower heart rate and blood pressure in beta-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.
Bijl
M J
MJ
Department of Epidemiology and Biostatistics, Erasmus Medical Center, Rotterdam, The Netherlands.
Visser
L E
LE
van Schaik
R H N
RH
Kors
J A
JA
Witteman
J C M
JC
Hofman
A
A
Vulto
A G
AG
van Gelder
T
T
Stricker
B H Ch
BH
D000319:Adrenergic beta-Antagonists / Q000378:metabolism* / Q000494:pharmacology / Q000627:therapeutic use*; D000368:Aged; D001794:Blood Pressure / Q000187:drug effects*; D003430:Cross-Sectional Studies; D019389:Cytochrome P-450 CYP2D6 / Q000235:genetics* / Q000378:metabolism*; D005260:Female; D005828:Genetics, Population / Q000379:methods*; D005838:Genotype; D006339:Heart Rate / Q000187:drug effects*; D006801:Humans; D006973:Hypertension / Q000188:drug therapy; D008297:Male; D008790:Metoprolol / Q000378:metabolism* / Q000494:pharmacology* / Q000627:therapeutic use; D009426:Netherlands; D011110:Polymorphism, Genetic
D000319:Adrenergic beta-Antagonists; D019389:Cytochrome P-450 CYP2D6; D008790:Metoprolol