β-blocker therapy and heart rate control during exercise testing in the general population: role of a common G-protein β-3 subunit variant.
OBJECTIVE
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.


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.


CONCLUSIONS
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.
Dörr
Marcus
M
Department of Internal Medicine B, Ernst-Moritz-Arndt University, Friedrich Loeffler Str. 23 a, D-17475 Greifswald, Germany. mdoerr@uni-greifswald.de
Schmidt
Carsten O
CO
Spielhagen
Thomas
T
Bornhorst
Alexa
A
Hentschel
Katharina
K
Franz
Christina
C
Empen
Klaus
K
Kocher
Thomas
T
Diehl
Scott R
SR
Kroemer
Heyo K
HK
Völzke
Henry
H
Ewert
Ralf
R
Felix
Stephan B
SB
Rosskopf
Dieter
D
D000319:Adrenergic beta-Antagonists / Q000627:therapeutic use*; D000328:Adult; D000368:Aged; D005080:Exercise Test; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D005838:Genotype; D006339:Heart Rate / Q000235:genetics*; D020962:Heterotrimeric GTP-Binding Proteins / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D011446:Prospective Studies; D021122:Protein Subunits; D012306:Risk
D000319:Adrenergic beta-Antagonists; C454420:G-protein beta3 subunit; D021122:Protein Subunits; D020962:Heterotrimeric GTP-Binding Proteins