β<sub>2</sub>-Adrenoceptor polymorphisms and asthma phenotypes: interactions with passive smoking

Wilson, Nicola; Bush, Andrew

doi:10.1183/09031936.00123206

Cited by 35 publications

(37 citation statements)

References 42 publications

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“…In the general linear model, there was no interaction between genotype and atopy, and no detectable effect of parental smoking. The present results confirm those of ZHANG et al [1], and suggest a sizeable effect since numbers in our study were small. The relevance of this is unclear, but the same occurrence in separate cohorts in different hemispheres suggests that they are real.…”

supporting

confidence: 92%

“…In the Australian unselected cohort, arginine (Arg) 16 was found to be associated with decreased lung function in children aged 11 yrs who had been exposed to passive smoking [1]. However, in the UK high-risk cohort (at least one atopic parent), no similar association was found for 10-yr-old children [2].…”

mentioning

confidence: 99%

“…With regard to the relationship between b 2 -AR polymorphisms and exhaled nitric oxide (eNO), we surmised that there were indirect links between b 2 -AR and eNO through cytokine regulation or endothelial L-arginine/nitric oxide pathway [1]. Interestingly, in the UK cohort, Arg16 and Glutamine (Gln) 27 were also found to be associated with decreased eNO.…”

mentioning

confidence: 99%

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Zhang¹,

Souëf²

2008

Eur Respir J

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confidence: 92%

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confidence: 99%

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Zhang¹,

Souëf²

2008

Eur Respir J

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“…[20][21][22] Tobacco smoke may also reduce β2AR density and ligand binding. 23 Besides these direct adverse effects of smoking on these respiratory outcomes and β2AR activity, a growing body of evidence also indicates that tobacco smoke exposures could modulate the effects of the Arg16Gly genotype on asthma, 7 lung function, 24 and AHR. 25 Additional research is warranted to examine the joint effects of Arg16Gly and tobacco smoke exposures on β2AR expression.…”

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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“…There is also conflicting evidence from studies examining the modifying effect of cigarette smoke on the associations between ADRB2 (beta-2 adrenergic receptor) polymorphisms and asthma (Zhang et al 2007). One explanation for the apparent contradictory results on the role of gene polymorphisms in the development of asthma between never and ever smokers was suggested by Litonjua et al (2004) who proposed that smoking has such a strong effect on airway hyperresponsiveness that may overwhelm any effects of ADRB2 variants.…”

Section: Discussionmentioning

confidence: 99%

Relationship between air pollution, NFE2L2 gene polymorphisms and childhood asthma in a Hungarian population

et al. 2011

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Air pollution and subsequent increased oxidative stress have long been recognized as contributing factors for asthma phenotypes. Individual susceptibility to oxidative stress is determined by genetic variations of the antioxidant defence system. In this study, we analysed the association between environmental nitrogen dioxide (NO 2 ) exposure and single nucleotide polymorphisms (SNP) in NFE2L2 and KEAP1 genes and their common impact on asthma risk.We genotyped 12 SNPs in a case-control study of 307 patients diagnosed with asthma and 344 controls. NO 2 concentration was collected from the period preceding the development of asthma symptoms. Multiple logistic regression was applied to evaluate the effects of the studied genetic variations on asthma outcomes in interaction with NO 2 exposure. Our data showed that genotypes of rs2588882 and rs6721961 in the regulatory regions of the NFE2L2 gene were inversely associated with infection-induced asthma (odds ratio (OR)00.290, p00.0015, and OR00.437, p0 0.007, respectively). Furthermore, case-only analyses revealed significant differences for these SNPs between asthma patients that lived in modestly or highly polluted environment , p 00.01, and OR 0 0.51, p00.02, respectively, in a dominant model). In conclusion, our results throw some new light upon the impact of NFE2L2 polymorphisms on infection-induced asthma risk and their effect in gene-environment interactions.

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β₂-Adrenoceptor polymorphisms and asthma phenotypes: interactions with passive smoking

Cited by 35 publications

References 42 publications

From the authors

From the authors

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

Relationship between air pollution, NFE2L2 gene polymorphisms and childhood asthma in a Hungarian population

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β2-Adrenoceptor polymorphisms and asthma phenotypes: interactions with passive smoking

Cited by 35 publications

References 42 publications

From the authors

From the authors

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

Relationship between air pollution, NFE2L2 gene polymorphisms and childhood asthma in a Hungarian population

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Resources

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β₂-Adrenoceptor polymorphisms and asthma phenotypes: interactions with passive smoking