American Journal of Epidemiology Advance Access published online on June 29, 2005
American Journal of Epidemiology, doi:10.1093/aje/kwi184
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1 Clinical Epidemiology Unit, Faculty of Medicine, Ramathibodi Hospital, Mahidol University, Bangkok, Thailand
* To whom correspondence should be addressed. A number of studies have investigated two common polymorphisms in the
Received January 17, 2005
Accepted March 14, 2005
HUMAN GENOME EPIDEMIOLOGY (HuGE) REVIEW
Systematic Review and Meta-Analysis of the Association between
2-Adrenoceptor Polymorphisms and Asthma: A HuGE Review
2 Centre for Clinical Epidemiology and Biostatistics, University of Newcastle, Newcastle, New South Wales, Australia
3 Centre for Biostatistics and Genetic Epidemiology, Department of Health Sciences, University of Leicester, Leicester, United Kingdom
4 Department of Respiratory and Sleep Medicine, Hunter Medical Research Institute, John Hunter Hospital, Newcastle, New South Wales, Australia
5 Department of Respiratory Medicine, Waikato Hospital, Hamilton, New Zealand
6 Queensland Institute of Medical Research, Brisbane, Queensland, Australia
7 Division of Therapeutics and Molecular Medicine, University Hospital, Nottingham, United Kingdom
8 Department of Environmental and Occupational Health Sciences, School of Public Health and Community Medicine, University of Washington, Seattle, WA
9 Department of Paediatrics, The Chinese University of Hong Kong, Hong Kong, Special Administrative Region, China
10 Department of Child Health, Medical School, University of Aberdeen, Aberdeen, United Kingdom
11 deCODE Genetics, Inc., Reykjavik, Iceland
12 Department of Genetics, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
John Attia, E-mail: John.Attia{at}newcastle.edu.au
Abstract 
2-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.
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