Wang Chengwei, Salam Muhammad T, Islam Talat, Wenten Madé, Gauderman W James, Gilliland Frank D
Department of Preventive Medicine, Keck School of Medicine, University of Southern California, 1540 Alcazar St, CHP 236, Los Angeles, CA 90033, USA.
Pediatrics. 2008 Jul;122(1):e107-14. doi: 10.1542/peds.2007-3370. Epub 2008 Jun 16.
Associations between single-nucleotide polymorphisms in the beta2-adrenergic receptor gene and asthma and wheeze have been inconsistent. Recent studies indicated that tobacco smoke affects beta2-adrenergic receptor gene expression and associations of beta2-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 beta2-adrenergic receptor gene on asthma and wheezing in 3128 non-Hispanic and Hispanic white children of the Children's Health Study.
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.
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.
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 beta2-adrenergic receptor gene variants on respiratory health outcomes.
β2 - 肾上腺素能受体基因单核苷酸多态性与哮喘及喘息之间的关联一直存在争议。近期研究表明，烟草烟雾会影响β2 - 肾上腺素能受体基因表达以及该基因变异与成人哮喘的关联。我们旨在研究子宫内及儿童期二手烟草烟雾暴露与β2 - 肾上腺素能受体基因的2个特征明确的功能性单核苷酸多态性（Arg16Gly和Glu27Gln）对儿童健康研究中3128名非西班牙裔和西班牙裔白人儿童哮喘及喘息的联合影响。
我们采用逻辑回归模型来估计这些单核苷酸多态性以及子宫内和二手烟草烟雾暴露对哮喘及喘息结局的独立和联合影响的比值比及95%置信区间。
子宫内母亲吸烟及二手烟草烟雾暴露与喘息相关。与未暴露且至少有1个Gly16等位基因的儿童相比，携带Arg16等位基因纯合子且在子宫内暴露于母亲吸烟的儿童终生喘息风险增加了两倍。我们发现二手烟草烟雾和Arg16Gly与喘息有类似的联合效应。在Arg16纯合子儿童中，终生、当前及夜间喘息风险随家中吸烟者数量增加而升高。1993年和1996年招募的2组儿童的结果一致。基于双倍型的分析与单核苷酸多态性特异性结果一致。未发现Glu27Gln有相关性。
子宫内及儿童期接触烟草烟雾均与儿童喘息风险增加相关，对于Arg16Arg基因型或Arg16 - Gln27双倍型2拷贝的儿童，风险更高。在评估β2 - 肾上腺素能受体基因变异对呼吸健康结局的影响时，需要考虑吸烟暴露情况。
