β-blocker therapy and heart rate control during exercise testing in the general population: role of a common G-protein β-3 subunit variant
| Autor: | Marcus Dörr, Katharina Hentschel, Thomas Spielhagen, Stephan B. Felix, Henry Völzke, Heyo K. Kroemer, Klaus Empen, Ralf Ewert, Christina Franz, Thomas D. Kocher, Carsten Oliver Schmidt, Alexa Bornhorst, Scott R. Diehl, Dieter Rosskopf |
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| Rok vydání: | 2010 |
| Předmět: |
Adult
Male Risk medicine.medical_specialty Genotype Adrenergic beta-Antagonists Population Biology Article Gene Frequency Heart Rate Polymorphism (computer science) Internal medicine Linear regression Heart rate Genetics medicine Humans Genetic Predisposition to Disease Prospective Studies Prospective cohort study education Allele frequency Aged Pharmacology education.field_of_study Polymorphism Genetic Confounding Genetic Variation Middle Aged Heterotrimeric GTP-Binding Proteins Protein Subunits Endocrinology Exercise Test Molecular Medicine Female GNB3 |
| Zdroj: | Pharmacogenomics. 11:1209-1221 |
| ISSN: | 1744-8042 1462-2416 |
| Popis: | Aim: Impaired heart rate (HR) response to exercise is associated with increased cardiovascular morbidity and mortality. We analyzed whether common variants (rs5443/C825T and rs5442/G814A) in the G-protein β3 subunit (GNB3) gene modulate interindividual variation in β-blocker responses with respect to HR. Materials & methods: Among 1614 subjects (347 current β-blocker users) of a population-based study, HR during symptom-limited exercise testing was analyzed by multilevel linear regression models adjusted for potential confounders. Results: In β-blocker users, but not in nonusers, HR was attenuated in rs5443 T allele carriers (TC/TT vs CC) with lower adjusted HR over the entire exercise period from rest to peak workload (3.5 bpm; 95% CI: 1.1–5.8; p < 0.01), and during recovery (4.2 bpm; 95% CI: 0.6–7.8; p = 0.02). The genotype-related HR reducing effect at peak exercise varied by up to 7.5 bpm (CC vs TT), more than a third (35.9%) of the total β-blocker effect (20.9 bpm). By contrast, rs5442 had no impact on any HR-related parameter. Conclusion: In this population-based sample, a common GNB3 polymorphism (C825T) was significantly related with response to β-blocker therapy with respect to HR during exercise and HR recovery, respectively. Further prospective studies are needed to confirm these associations and to examine their potential clinical relevance. |
| Databáze: | OpenAIRE |
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