Abstract
BackgroundGrowing evidence suggests that the Arg16Arg genotype of the beta-2 adrenergic receptor gene may be associated with adverse effects of beta-agonist therapy. We sought to examine the association of beta-agonist use and the Arg16Gly polymorphism with lung function and mortality among participants in the Atherosclerosis Risk in Communities study.Methodology and Principal FindingsWe genotyped study participants and analyzed the association of the Arg16Gly polymorphism and beta-agonist use with lung function at baseline and clinical examination three years later and with all-cause mortality during 10 years of follow-up. Lung function was characterized by percent-predicted forced expiratory volume in 1 second. Associations were examined separately for blacks and whites. Black beta-agonist users with the Arg/Arg genotype had better lung function at baseline and at the second clinical visit than those with Arg/Gly and Gly/Gly genotypes. Adjusted mean percent-predicted FEV1 was 21% higher in Arg/Arg subjects compared to Gly/Gly at baseline (p = 0.01) and 20% higher than Gly/Gly at visit 2 (p = 0.01). Arg/Gly subjects had adjusted percent-predicted FEV1 17% lower than Arg/Arg at baseline but were similar to Arg/Arg subjects at visit 2. Although black beta-agonist users with the Arg/Arg genotype appeared to have better crude survival rates, the association between genotype and all-cause mortality was inconclusive. We found no difference in lung function or mortality by genotype among blacks who did not use beta-agonists or among whites, regardless of beta-agonist use.ConclusionsBlack beta-agonist users with the ADRB2 Arg16Arg genotype had better lung function, and, possibly, better overall survival compared to black beta-agonist users with the Gly16Gly genotype. Our findings highlight the need for additional studies of sufficient size and statistical power to allow examination of outcomes among beta-agonist users of different races and genotypes.
Highlights
Asthma is an important cause of morbidity and mortality in the United States, where African-Americans bear a disproportionate burden of asthma hospitalization and have asthma mortality rates 3 to 4 times higher than whites[1]
This is the first large, population-based study to examine the association between ADRB2 Arg16Gly polymorphism, lung function, beta-agonist use, and mortality
We observed no differences in survival by genotype among black or white subjects not reporting beta-agonist use at visit 2. This is the first large, population-based study to examine the association between ADRB2 Arg16Gly polymorphism, beta-agonist use, lung function, and mortality
Summary
Asthma is an important cause of morbidity and mortality in the United States, where African-Americans bear a disproportionate burden of asthma hospitalization and have asthma mortality rates 3 to 4 times higher than whites[1]. Recent studies, including a randomized clinical trial, indicate that asthma patients with the Arg/Arg genotype may experience adverse effects from beta-agonist use, including deterioration of lung function [10,11,12,13,14,15,16], and recent literature reviews suggest an emerging consensus that the Arg allele is associated with clinically significant, unsatisfactory response to beta-agonists [17,18,19,20,21]. We genotyped study participants and analyzed the association of the Arg16Gly polymorphism and beta-agonist use with lung function at baseline and clinical examination three years later and with all-cause mortality during 10 years of follow-up. Our findings highlight the need for additional studies of sufficient size and statistical power to allow examination of outcomes among beta-agonist users of different races and genotypes
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