Abstract 766: Effect Of The Arg389Gly-Polymorphism On Exercise-Induced Tachycardia: Genotype-Effects Are Subject To A Diurnal Variation
Rationale: We investigated effects of the adrenergic β1-receptor Arg389Gly polymorphism. The Gly-allele is a minus-variant (e.g. Gly-homozygotes show less inotropic dobutamine-response). However, studies on the impact of the polymorphism on exercise-induced tachycardia yielded controversial results.
Hypothesis: In a double-blind cross-over trial we investigated whether Arg/Arg and Gly/Gly homozygotes differ in exercise-induced tachycardia after placebo(Pla) or bisoprolol(Bis).
Methods: We studied 14 homozygous male volunteers (7 Arg/Arg, 7 Gly/Gly) matched for age, sport-activity, and weight. A single dose of Pla and Bis(10 mg) were administered between 6.00 and 7.30 a.m. Treatment phases were separated by a washout-period of ≥1 week. During each treatment phase, 3 bicycle tests were performed in supine position (from 50 to 175 W; 2.5h, 10h & 26h after drug-challenge). The heart rate increase caused by work load escalation was analysed by linear regression.
Results: In the Pla-phase, exercise-induced tachycardia was higher in Arg389-homozygotes in both morning-tests (2.5 & 26h; p <0.01 vs. Gly/Gly; Fig. A⇓). Notably, this difference was undetectable in the afternoon test (p=0.3; Fig. B⇓). The absolute heart rates after Bis did not differ between genotypes in the tests at 2.5h & 10h. However, the difference reappeared at the time-point with the lowest Bis-levels (26h; p <0.01).
Conclusions: In the absence of β-blockade, Gly-homozygotes show less exercise-induced tachycardia as compared to Arg-homozygotes. This genotype-effect may be abolished by circadian interference. This diurnal variation likely contributed to the discrepancy of previously reported results.