Influence of beta2-adrenergic receptor genotype on airway function during exercise in healthy adults.
BACKGROUND
In humans, beta(2)-adrenergic receptors (beta(2)ARs) influence airway tone. There are known functional polymorphisms of the beta(2)AR, 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 [Vo(2)], 32 +/- 2 mL/kg/min) or the Gly16 allele (n = 26; mean age, 30 +/- 1 years; mean maximum Vo(2), 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 Vo(2) 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 (FEF(50)). FEF(50) 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 FEF(50) = + 7 +/- 2% over pre-exercise) while the Arg16 subjects had a rapid return to baseline (10 min after FEF(50) = - 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 beta(2)AR 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.
Snyder
Eric M
EM
Gonda 5-369, Mayo Clinic and Foundation, 200 First Street SW, Rochester, MN 55905, USA.
Beck
Kenneth C
KC
Dietz
Niki M
NM
Joyner
Michael J
MJ
Turner
Stephen T
ST
Johnson
Bruce D
BD
D000328:Adult; D001120:Arginine / Q000235:genetics; D001980:Bronchi / Q000502:physiology*; D004837:Epinephrine / Q000032:analysis; D015444:Exercise / Q000502:physiology*; D005080:Exercise Test; D005260:Female; D005838:Genotype; D005998:Glycine / Q000235:genetics; D006801:Humans; D008297:Male; D009638:Norepinephrine / Q000032:analysis; D020641:Polymorphism, Single Nucleotide / Q000502:physiology*; D018343:Receptors, Adrenergic, beta-2 / Q000235:genetics*; D015656:Respiratory Mechanics / Q000502:physiology*
D018343:Receptors, Adrenergic, beta-2; D001120:Arginine; D005998:Glycine; D009638:Norepinephrine; D004837:Epinephrine