Genetic variation in the CYP2D6 gene is associated with a lower heart rate and blood pressure in beta-blocker users.
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Bijl MJ, Visser LE, van Schaik RH, Kors JA, Witteman JC, Hofman A, Vulto AG, van Gelder T, Stricker BH
Genetic variation in the CYP2D6 gene is associated with a lower heart rate and blood pressure in beta-blocker users.
Clin Pharmacol Ther. 2009 Jan;85(1):45-50. doi: 10.1038/clpt.2008.172. Epub 2008 Sep 10.
- PubMed ID
- 18784654 [ View in PubMed]
- Abstract
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.
DrugBank Data that Cites this Article
- Pharmaco-genomics
Drug Interacting Gene/Enzyme Allele name Genotypes Defining change(s) Type(s) Description Details Metoprolol Cytochrome P450 2D6
Gene symbol: CYP2D6
UniProt: P10635CYP2D6*4 (A;A) - A allele (rs3892097)
Directly Studied Effect Patients with this genotype have reduced metabolism of metoprolol. Details