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Influence of p2-Adrenergic Receptor Genotype on Airway Function During Exercise in Healthy Adults: Study Limitations

Published in Pulmonary Function

We only investigated the role of a single-nucleotide polymorphism (SNP) on physiologic function. Previous work by Drysdale and colleagues sequenced the entire P2AR in a large population of asthmatics. They subsequently grouped the SNPs according to haplotypes; and while no SNP was associated with response to a P-agonist, combinations of SNPs grouped according to haplotype pairs did predict P-agonist responsiveness. Thus, it is possible that grouping subjects according to P2AR haplotype may more accurately predict the airway changes during and after exercise. Other stud-ies have suggested that position 27 may also play a role in modulating receptor function. When we examined the influence of variation at position 27, the homozygous Gly16/Gln27 haplotype tended to have the largest changes in FEF50 during heavy exercise, followed by the Gly16Gly/Gln27Glu combination, the homozygous Arg16/Gln27 group, and finally the homozygous Gly16/Glu27 haplotype, suggesting that Gln at position 27 may be more catecholamine sensitive. However, none of the differences that were observed at 5 min and 10 min of recovery could be explained by position 27. Another limitation of this study was the small sample size in light of the inherent difficulties in identifying subtle changes in airway tone both during and in the recovery phase of exercise in healthy adults and the likely small influence of common polymorphisms of the P2AR on airway smooth-muscle function. http://buy-asthma-inhalers-online.com/advair-diskus-inhaler-fluticasone-salmeterol.html

In conclusion, we found that healthy subjects homozygous for Arg16 or Gly16 of the B2AR had similar bronchodilatory responses during short-dura-tion exercise. However, the airway tone in Arg16 subjects returned to baseline rapidly after exercise, while Gly16 subjects maintained sustained bron-chodilation, as measured by FEF50. This suggests that subjects homozygous for the Arg16 polymorphism have enhanced desensitization of the B2AR. This may have implications in the study of exercise-induced bronchospasm and the response to exercise in patients with asthma, in whom changes in airway function are most prominent after exercise.