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

PLoS One. 2007 Mar 14;2(3):e289. doi: 10.1371/journal.pone.0000289.


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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Amino Acid Substitution*
  • Atherosclerosis / epidemiology*
  • Atherosclerosis / mortality*
  • Cohort Studies
  • Female
  • Follow-Up Studies
  • Humans
  • Lung / physiology*
  • Lung / physiopathology
  • Male
  • Middle Aged
  • Mutation, Missense
  • Polymorphism, Genetic*
  • Probability
  • Receptors, Adrenergic, beta-2 / genetics*
  • Respiratory Function Tests
  • Risk Factors
  • Smoking / epidemiology
  • United States / epidemiology


  • Receptors, Adrenergic, beta-2