Systematic review and meta-analysis of the association between β2-adrenoceptor polymorphisms and asthma: A HuGE review

Ammarin Thakkinstian, Mark McEvoy, Cosetta Minelli, Peter Gibson, Bob Hancox, David Duffy, John Thompson, Ian Hall, Joel Kaufman, Ting Fan Leung, Peter Joseph Helms, Hakon Hakonarson, Eva Halpi, Ruth Navon, John Attia

Research output: Contribution to journalReview articlepeer-review

Abstract

A number of studies have investigated two common polymorphisms in the β2-adrenoceptor gene, Arg/Gly16 and Gln/Glu27, in relation to asthma susceptibility. The authors performed a meta-analysis of each polymorphism, as well as haplotype analysis, for adult and pediatric populations separately, using published data, supplemented by additional data requested from the original authors. Individual analysis detected no effect of Arg/Gly16 in adults but did suggest a recessive protective effect of Gly16 for children, with an odds ratio of 0.71 (95% confidence interval (CI): 0.53, 0.96) compared with the other genotypes. Results for Gln/Glu27 in adults seem to indicate that heterozygotes are at decreased risk of asthma than either homozygote (odds ratio = 0.73, 95% CI: 0.62, 0.87), although the studies are heterogeneous; in children, the Glu/Glu genotype has a decreased risk of asthma (odds ratio = 0.60, 95% CI: 0.35, 0.99) compared with the other genotypes. Despite the proximity of these two polymorphic sites, the linkage disequilibrium coefficient of 0.41 was not high (p < 0.001). Haplotype analysis suggests that there may be an interaction between the two sites, with a lower risk of asthma associated with the Glu27 allele (compared with Gln27), and that this risk is modified by the allele at position 16.

Original languageEnglish
Pages (from-to)201-211
Number of pages11
JournalAmerican Journal of Epidemiology
Volume162
Issue number3
DOIs
StatePublished - Aug 2005

Keywords

  • Asthma
  • Epidemiology
  • Genetics
  • Haplotypes
  • Linkage disequilibrium
  • Meta-analysis
  • Polymorphism, genetic
  • Receptors, adrenergic

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