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Influence of ß₂-Adrenergic Receptor Genotype on Airway Function During Exercise in Healthy Adults^*

^* From the Departments of Internal Medicine (Drs. Snyder, Beck, Turner, and Johnson) and Anesthiology (Drs. Dietz and Joyner), Mayo Clinic and Foundation, Rochester, MN.

Correspondence to: Bruce D. Johnson, PhD, Associate Professor of Medicine, Gonda 5-369, Mayo Clinic and Foundation, 200 First St, SW, Rochester, MN 55905; e-mail: johnson.bruce{at}mayo.edu

Abstract

Background: In humans, ß₂-adrenergic receptors (ß₂ARs) influence airway tone. There are known functional polymorphisms of the ß₂AR, such as substitution of glycine for arginine at codon 16. We sought to determine if this variation in genotype differentially influences airway function during exercise.

Methods: Healthy subjects without asthma who were either homozygous for Arg16 (n = 16; mean age, 29 ± 2 years [± SD]; mean maximum oxygen uptake [O₂], 32 ± 2 mL/kg/min) or the Gly16 allele (n = 26; mean age, 30 ± 1 years; mean maximum O₂, 33 ± 1 mL/kg/min) participated in the study. Baseline testing included spirometry and maximal symptom-limited exercise. On a separate day, an arterial cannula was placed to measure catecholamine levels. Subjects then performed exercise at two work levels (40% and 75% of peak work) for 9 min each and performed spirometry at 3-min intervals for assessment of airway function.

Results: There were no statistically significant differences between groups in maximum O₂ or baseline spirometry (p > 0.05). With both light and heavy exercise, the groups had similar increases in the forced expiratory flow at 50% of vital capacity (FEF₅₀). FEF₅₀ increased by 14 ± 4% and 15 ± 3% in arginine and glycine groups, respectively, by end exercise (p > 0.05). During recovery (5 min and 10 min after), the Gly16 homozygotes demonstrated persistent bronchodilation (10 min after FEF₅₀ = + 7 ± 2% over pre-exercise) while the Arg16 subjects had a rapid return to baseline (10 min after FEF₅₀ = – 3 ± 3%, p = 0.007 between groups). No differences were observed in the catecholamine responses between genotypes, although the increase in epinephrine in the arginine group tended to be higher (p = 0.07).

Conclusions: These data suggest that the Arg16Gly polymorphism of the ß₂AR does not influence airway function during short-duration low- and high-intensity exercise. However, during recovery, the Arg16 genotype is associated with a reduced bronchodilation, possibly due to increased catecholamine desensitization.

Key Words: bronchodilation • catecholamines • genetic

This article has been cited by other articles:

				E. M. Snyder, S. T. Turner, and B. D. Johnson {beta}2-Adrenergic Receptor Genotype and Pulmonary Function in Patients With Heart Failure. Chest, November 1, 2006; 130(5): 1527 - 1534. [Abstract] [Full Text] [PDF]