β2-adrenergic receptor polymorphisms are associated with asthma and COPD in adults

Matheson, Melanie C.; Ellis, Justine A.; Raven, Joan; Johns, DP; Walters, E. Haydn; Abramson, Michael J.

doi:10.1007/s10038-006-0043-z

Cited by 46 publications

(48 citation statements)

References 43 publications

(60 reference statements)

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“…11,12 Because the effects of these SNPs and smoking exposures on asthma/ wheeze were similar within each ethnic group (data not shown; available on request), we conducted pooled analyses. Logistic regression models were fitted to compute odds ratios (ORs) and 95% confidence intervals (95% CIs).…”

Section: Discussionmentioning

confidence: 99%

Effects of In Utero and Childhood Tobacco Smoke Exposure and β2-Adrenergic Receptor Genotype on Childhood Asthma and Wheezing

et al. 2008

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Objective-Associations between single-nucleotide polymorphisms in the β2-adrenergic receptor gene and asthma and wheeze have been inconsistent. Recent studies indicated that tobacco smoke affects β2-adrenergic receptor gene expression and associations of β2-adrenergic receptor gene variants with asthma in adults. We aimed to investigate the joint effects of in utero and childhood secondhand tobacco smoke exposure and 2 well-characterized functional single-nucleotide polymorphisms (Arg16Gly and Glu27Gln) of β2-adrenergic receptor gene on asthma and wheezing in 3128 non-Hispanic and Hispanic white children of the Children's Health Study.Methods-We fitted logistic regression models to estimate odds ratios and 95% confidence intervals for the independent and joint effects of these single-nucleotide polymorphisms and in utero and secondhand tobacco smoke exposure on asthma and wheeze outcomes.Results-Exposures to in utero maternal smoking and secondhand tobacco smoke were associated with wheezing. Children who were homozygous for the Arg16 allele and were exposed to maternal smoking in utero were at a threefold increased risk for lifetime wheeze compared with children who were unexposed and had at least 1 Gly16 allele. We found similar joint effects of secondhand tobacco smoke and Arg16Gly with wheezing. The risk for lifetime, current, and nocturnal wheeze increased with the number of smokers at home among Arg16 homozygous children. The results were consistent in 2 cohorts of children recruited in 1993 and 1996. Diplotype-based analyses were consistent with the single-nucleotide polymorphism-specific results. No associations were found for Glu27Gln.Conclusions-Both in utero and childhood exposure to tobacco smoke were associated with an increased risk for wheeze in children, and the risks were greater for children with the Arg16Arg genotype or 2 copies of the Arg16-Gln27 diplotype. Exposures to smoking need to be taken into account when evaluating the effects of β2-adrenergic receptor gene variants on respiratory health outcomes. In ADRB2, Arg16Gly and Glu27Gln are the 2 most common nonsynonymous single-nucleotide polymorphisms (SNPs). In an in vitro study, Green et al 1 found that the Gly16 allele was more susceptible to agonist-promoted downregulation, and the Glu27 allele was resistant to agonistmediated receptor downregulation; however, subsequent ex vivo and in vivo studies provided inconsistent findings. 2 The majority of the epidemiologic studies have investigated the associations of these 2 SNPs and asthma/wheeze and found inconsistent results. In addition, meta-analyses that pooled data from these studies failed to show any significant associations with asthma; however, these authors could not rule out effects of these SNPs on asthma symptoms. [3][4][5][6] The inconsistencies across studies may have resulted from not taking into account environmental factors that could modulate the receptor activity. Tobacco smoke is 1 such factor that is associated with an increase in AHR and oxidant stress-mediated...

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Section: Discussionmentioning

confidence: 99%

Effects of In Utero and Childhood Tobacco Smoke Exposure and β2-Adrenergic Receptor Genotype on Childhood Asthma and Wheezing

et al. 2008

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“…There is extensive evidence that susceptibility / resistance to smoking-induced airway disorders is genetically determined [6][7][8][9][10][11][12][13][14]40 . Family studies confirm there is a heritable component of COPD 41 .…”

Section: Implication Of Airway Gene Expression Variability For Genesimentioning

confidence: 99%

“…are genes that give susceptibility to, or protect from, the stress that smoking places on the airways, and that together, mediate whether the individual smoker does or does not develop COPD [6][7][8][9] . However, while progress has been made, the identification of these genes has proven to be a significant challenge, as there are likely many genes involved, complicated by issues such as ancestral diversity, variability of smoking exposures, and the false discovery rate when assessing all 25,000 genes in the human genome [10][11][12][13][14] .…”

Section: Introductionmentioning

confidence: 99%

“…The present study is directed toward a novel approach to identify possible candidate genes for susceptibility to smoking-induced lung disease that should be complementary to the strategies of family-based and genome wide association studies [6][7][8][9][10][11][12][13][14][15][16][17] . Our strategy, derived from the observation of variability of gene expression in the human airway epithelium [18][19][20] , is based on the following concepts: (1) the airway epithelium is the cell population that takes the brunt of the stress of cigarette smoke; (2) disease of the small airway epithelium is an early component of the development of COPD [1][2][3][21][22][23] ; and (3) the increasing evidence that genetic susceptibility to complex disorders is mediated by polymorphisms in multiple protective/susceptibility genes resulting in over-and under-expression of gene products that together, mediate protection from, or the development of, disease [11][12][13][14][24][25][26] .…”

Section: Introductionmentioning

confidence: 99%

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Variability in Small Airway Epithelial Gene Expression Among Normal Smokers

Ammous

Hackett

Butler

et al. 2008

Chest

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SummaryBackground-Despite overwhelming data that cigarette smoking causes chronic obstructive pulmonary disease (COPD), only a minority of chronic smokers are affected, strongly suggesting that genetic factors modify susceptibility to this disease. We hypothesized that there are individual variations in the response to cigarette smoking, with variability among smokers in expression levels of protective / susceptibility genes.

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“…The results of such studies on disease risk and treatment response result in conflicting results [3][4][5][6][7][8]. Specific ADRB2 polymorphisms may be associated with COPD structural lung disease, disease control and drug specific response to therapy [9][10][11][12][13][14]. Variable ADRB2 study designs have yielded conflicting data in the past decade.…”

Section: Introductionmentioning

confidence: 99%

No Correlation between Beta2-Adrenergic Receptor Polymorphisms and the Severity and Clinical Control of Geriatric Asthma and COPD

Pham¹

2014

J Allergy Ther

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Background: Polymorphisms of the β2-adrenergic receptor (ADRB2) have previously been associated with non-specific bronchial hyper-responsiveness, adverse response to β2-agonists and variable effects on lung function. The objective of this study was to determine whether genotypic variance in ADRB2 polymorphisms in a cohort of geriatric men and women with asthma and/or COPD correlate with disease severity, baseline pulmonary function, and the ability to maintain clinical control of their disease.Methods: This comparative, prospective cohort study sequenced two ADRB2 polymorphisms, Arg16 --> Gly and Gln27 --> Glu, in 103 geriatric patients with a clinical history of asthma and/or COPD. Primary endpoints included pulmonary exacerbation rate, hospitalization rate, and quality of life scores.Results: Arg/Arg genotype comprised 13.6% of the cohort. No significant differences in baseline pulmonary functions were noted across genotypic variants. No significant difference was associated with genotype and change in lung function, exacerbations, clinical hospitalizations, exercise tolerance and subjective quality of life assessment over 6 months of follow-up. Conclusion:We conclude that in a geriatric asthma and/or COPD population, ADRB2 polymorphisms are not a factor in the ability to control disease.

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β2-adrenergic receptor polymorphisms are associated with asthma and COPD in adults

Cited by 46 publications

References 43 publications

Effects of In Utero and Childhood Tobacco Smoke Exposure and β2-Adrenergic Receptor Genotype on Childhood Asthma and Wheezing

Effects of In Utero and Childhood Tobacco Smoke Exposure and β2-Adrenergic Receptor Genotype on Childhood Asthma and Wheezing

Variability in Small Airway Epithelial Gene Expression Among Normal Smokers

No Correlation between Beta2-Adrenergic Receptor Polymorphisms and the Severity and Clinical Control of Geriatric Asthma and COPD

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