Β-blocker therapy and heart rate control during exercise testing in the general population: Role of a common G-protein Β-3 subunit variant

Marcus Dörr, Carsten O. Schmidt, Thomas Spielhagen, Alexa Bornhorst, Katharina Hentschel, Christina Franz, Klaus Empen, Thomas Kocher, Scott R. Diehl, Heyo K. Kroemer, Henry Völzke, Ralf Ewert, Stephan B. Felix, Dieter Rosskopf

Research output: Contribution to journalArticlepeer-review

9 Scopus citations

Abstract

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-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-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-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-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.

Original languageEnglish (US)
Pages (from-to)1209-1221
Number of pages13
JournalPharmacogenomics
Volume11
Issue number9
DOIs
StatePublished - Sep 2010

All Science Journal Classification (ASJC) codes

  • Molecular Medicine
  • Genetics
  • Pharmacology

Keywords

  • GNB3
  • epidemiology
  • exercise testing
  • genetic susceptibility
  • heart rate
  • polymorphism
  • Β-blocker

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