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ADRB2 Arg16Gly polymorphism, lung function, and mortality: results from the Atherosclerosis Risk in Communities study.

Ferdinands JM, Mannino DM, Gwinn ML, Bray MS - PLoS ONE (2007)

Bottom Line: Growing evidence suggests that the Arg16Arg genotype of the beta-2 adrenergic receptor gene may be associated with adverse effects of beta-agonist therapy.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.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.

View Article: PubMed Central - PubMed

Affiliation: Air Pollution and Respiratory Health Branch, Division of Environmental Hazards and Health Effects, National Center for Environmental Health, Centers for Disease Control and Prevention, Atlanta, Georgia, United States of America. zdn5@cdc.gov

ABSTRACT

Background: Growing 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 findings: 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. 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 FEV(1) 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 FEV(1) 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.

Conclusions: Black 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.

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Related in: MedlinePlus

Crude survival among black (upper panel, nā€Š=ā€Š63, pā€Š=ā€Š0.33) and white (lower panel, nā€Š=ā€Š189, pā€Š=ā€Š0.27) study participants reporting baseline beta-agonist use by ADRB2 Arg16Gly genotype
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pone-0000289-g002: Crude survival among black (upper panel, nā€Š=ā€Š63, pā€Š=ā€Š0.33) and white (lower panel, nā€Š=ā€Š189, pā€Š=ā€Š0.27) study participants reporting baseline beta-agonist use by ADRB2 Arg16Gly genotype

Mentions: Subjects were followed for an average of 9.9 years. Number of deaths and average length of follow-up by race and genotype, stratified by baseline beta-agonist use, are presented in Table 4. Among black subjects using beta-agonists at baseline, 18% of those with Arg/Arg died during follow-up compared with 29% of those with Arg/Gly and 41% of subjects with Gly/Gly (25th percentile survival time of>10 years for Arg/Arg, 9.0 years for Arg/Gly, and 5.5 years for Gly/Gly). This difference in crude mortality rates by genotype (Fig. 2) was not statistically significant (pā€Š=ā€Š0.33). Among white subjects reporting beta-agonist use at baseline, 22% of those with Arg/Arg died during follow-up compared to 25% with Arg/Gly and 27% with Gly/Gly (pā€Š=ā€Š0.27). We found no evidence of a difference in survival rates by genotype among blacks or whites who did not use beta-agonists. Controlling for age, sex, baseline FEV1/FVC ratio, baseline respiratory symptom score, and baseline smoking status, blacks using beta-agonists at baseline with the Arg/Gly genotype had better survival than black beta-agonist users with other genotypes [hazard ratio of 2.5 for Arg/Arg compared to Arg/Gly and 5.4 for Gly/Gly compared to Arg/Gly, pā€Š=ā€Š0.04]. Crude and adjusted hazard ratios by race and beta-agonist use are presented in Table 5.


ADRB2 Arg16Gly polymorphism, lung function, and mortality: results from the Atherosclerosis Risk in Communities study.

Ferdinands JM, Mannino DM, Gwinn ML, Bray MS - PLoS ONE (2007)

Crude survival among black (upper panel, nā€Š=ā€Š63, pā€Š=ā€Š0.33) and white (lower panel, nā€Š=ā€Š189, pā€Š=ā€Š0.27) study participants reporting baseline beta-agonist use by ADRB2 Arg16Gly genotype
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC1808432&req=5

pone-0000289-g002: Crude survival among black (upper panel, nā€Š=ā€Š63, pā€Š=ā€Š0.33) and white (lower panel, nā€Š=ā€Š189, pā€Š=ā€Š0.27) study participants reporting baseline beta-agonist use by ADRB2 Arg16Gly genotype
Mentions: Subjects were followed for an average of 9.9 years. Number of deaths and average length of follow-up by race and genotype, stratified by baseline beta-agonist use, are presented in Table 4. Among black subjects using beta-agonists at baseline, 18% of those with Arg/Arg died during follow-up compared with 29% of those with Arg/Gly and 41% of subjects with Gly/Gly (25th percentile survival time of>10 years for Arg/Arg, 9.0 years for Arg/Gly, and 5.5 years for Gly/Gly). This difference in crude mortality rates by genotype (Fig. 2) was not statistically significant (pā€Š=ā€Š0.33). Among white subjects reporting beta-agonist use at baseline, 22% of those with Arg/Arg died during follow-up compared to 25% with Arg/Gly and 27% with Gly/Gly (pā€Š=ā€Š0.27). We found no evidence of a difference in survival rates by genotype among blacks or whites who did not use beta-agonists. Controlling for age, sex, baseline FEV1/FVC ratio, baseline respiratory symptom score, and baseline smoking status, blacks using beta-agonists at baseline with the Arg/Gly genotype had better survival than black beta-agonist users with other genotypes [hazard ratio of 2.5 for Arg/Arg compared to Arg/Gly and 5.4 for Gly/Gly compared to Arg/Gly, pā€Š=ā€Š0.04]. Crude and adjusted hazard ratios by race and beta-agonist use are presented in Table 5.

Bottom Line: Growing evidence suggests that the Arg16Arg genotype of the beta-2 adrenergic receptor gene may be associated with adverse effects of beta-agonist therapy.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.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.

View Article: PubMed Central - PubMed

Affiliation: Air Pollution and Respiratory Health Branch, Division of Environmental Hazards and Health Effects, National Center for Environmental Health, Centers for Disease Control and Prevention, Atlanta, Georgia, United States of America. zdn5@cdc.gov

ABSTRACT

Background: Growing 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 findings: 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. 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 FEV(1) 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 FEV(1) 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.

Conclusions: Black 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.

Show MeSH
Related in: MedlinePlus