Systematic Review and Meta-Analysis of the Association between {beta}2-Adrenoceptor Polymorphisms and Asthma: A HuGE Review

A. Thakkinstian, M. McEvoy, C. Minelli, P. H. Gibson, B. Hancox, D. Duffy, J. Thompson, I. Hall, J. Kaufman, T. F. Leung, Peter Joseph Benedict Helms, H. Hakonarson, E. Halpi, R. Navon, J. Attia

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Abstract

A number of studies have investigated two common polymorphisms in the beta(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.

Original languageEnglish
Pages (from-to)201-211
Number of pages10
JournalAmerican Journal of Epidemiology
Volume162
Issue number3
DOIs
Publication statusPublished - 2005

Keywords

  • asthma
  • epidemiology
  • genetics
  • haplotypes
  • linkage disequilibrium
  • meta
  • analysis
  • polymorphism
  • genetic
  • receptors
  • adrenergic
  • RECEPTOR GENE POLYMORPHISM
  • BETA-2-ADRENERGIC RECEPTOR
  • MOLECULAR ASSOCIATION
  • ADRENOCEPTOR POLYMORPHISMS
  • ARG16GLY POLYMORPHISM
  • BETA(2) ADRENOCEPTOR
  • CHILDHOOD ASTHMA
  • RISK-FACTORS
  • POPULATION
  • HETEROGENEITY

Cite this

Systematic Review and Meta-Analysis of the Association between {beta}2-Adrenoceptor Polymorphisms and Asthma: A HuGE Review. / Thakkinstian, A.; McEvoy, M.; Minelli, C.; Gibson, P. H.; Hancox, B.; Duffy, D.; Thompson, J.; Hall, I.; Kaufman, J.; Leung, T. F.; Helms, Peter Joseph Benedict; Hakonarson, H.; Halpi, E.; Navon, R.; Attia, J.

In: American Journal of Epidemiology, Vol. 162, No. 3, 2005, p. 201-211.

Research output: Contribution to journalArticle

Thakkinstian, A, McEvoy, M, Minelli, C, Gibson, PH, Hancox, B, Duffy, D, Thompson, J, Hall, I, Kaufman, J, Leung, TF, Helms, PJB, Hakonarson, H, Halpi, E, Navon, R & Attia, J 2005, 'Systematic Review and Meta-Analysis of the Association between {beta}2-Adrenoceptor Polymorphisms and Asthma: A HuGE Review', American Journal of Epidemiology, vol. 162, no. 3, pp. 201-211. https://doi.org/10.1093/aje/kwi184
Thakkinstian, A. ; McEvoy, M. ; Minelli, C. ; Gibson, P. H. ; Hancox, B. ; Duffy, D. ; Thompson, J. ; Hall, I. ; Kaufman, J. ; Leung, T. F. ; Helms, Peter Joseph Benedict ; Hakonarson, H. ; Halpi, E. ; Navon, R. ; Attia, J. / Systematic Review and Meta-Analysis of the Association between {beta}2-Adrenoceptor Polymorphisms and Asthma: A HuGE Review. In: American Journal of Epidemiology. 2005 ; Vol. 162, No. 3. pp. 201-211.
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abstract = "A number of studies have investigated two common polymorphisms in the beta(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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AU - Thakkinstian, A.

AU - McEvoy, M.

AU - Minelli, C.

AU - Gibson, P. H.

AU - Hancox, B.

AU - Duffy, D.

AU - Thompson, J.

AU - Hall, I.

AU - Kaufman, J.

AU - Leung, T. F.

AU - Helms, Peter Joseph Benedict

AU - Hakonarson, H.

AU - Halpi, E.

AU - Navon, R.

AU - Attia, J.

PY - 2005

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N2 - A number of studies have investigated two common polymorphisms in the beta(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.

AB - A number of studies have investigated two common polymorphisms in the beta(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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KW - genetics

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KW - receptors

KW - adrenergic

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KW - MOLECULAR ASSOCIATION

KW - ADRENOCEPTOR POLYMORPHISMS

KW - ARG16GLY POLYMORPHISM

KW - BETA(2) ADRENOCEPTOR

KW - CHILDHOOD ASTHMA

KW - RISK-FACTORS

KW - POPULATION

KW - HETEROGENEITY

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DO - 10.1093/aje/kwi184

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SP - 201

EP - 211

JO - American Journal of Epidemiology

JF - American Journal of Epidemiology

SN - 0002-9262

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