Pharmacogenetic Effects of Inhaled Salbutamol on 10-km Time Trial Performance in Competitive Male and Female Cyclists.

ABSTRACT

OBJECTIVE: To determine the effects of single nucleotide polymorphisms (SNPs) in the adrenergic ß2-receptor gene (ADRB2, rs1042713, and rs1042714) and epithelial Na channel gene (SCNN1A, rs2228576) on cycling performance after the inhalation of salbutamol. DESIGN: Randomized double-blind, mixed-model repeated measures. SETTING: University Research Setting. PARTICIPANTS: Sixty-nine trained (maximal oxygen consumption 62.3 ± 7.6 mL·kg·min) male and female cyclists, aged 19 to 40 years. INTERVENTIONS: Participants performed two 10-km time trials 60 minutes after the inhalation of 400 µg of salbutamol or placebo. Subjects were genotyped for the three SNPs (rs1042713 AA 8, AG 30 GG 31; rs1042714 CC 19, CG 35, GG 15; rs2228576 GG 31 GA 34 AA 4). MAIN OUTCOME MEASURES: Forced expiratory volume in 1 second (FEV1) was assessed immediately before and 30 minutes after inhalation. Performance was measured by mean power output maintained over the duration of the time trial. RESULTS: There was a significant increase in FEV1 after the inhalation of salbutamol [mean (SD) = 5.68% (4.7)] compared with placebo [0.84% (2.8); P < 0.001]; however, this did not lead to an improvement in 10-km cycling time trial performance. Neither the bronchodilatory response nor the time trial performance after salbutamol was affected by genotype at any of the 3 SNPs. CONCLUSIONS: In cyclists, FEV1 was significantly improved after salbutamol administration regardless of genotypic variation at the ADRB2 (rs1042713 and rs1042714) and SCNN1A (rs2228576) genes. Despite this improvement in lung function, 10-km time trial performance was not altered after the inhalation of salbutamol. CLINICAL RELEVANCE Our findings did not show genotype-dependent differences in bronchodilatory responses and athletic performance to inhaled salbutamol, suggesting that genotype-specific drug therapy will not improve asthmatic athletes' care nor athletic performance.