Parental smoking modifies the relation between genetic variation in tumor necrosis factor-alpha (TNF) and childhood asthma.
Parental smoking modifies the relation between genetic variation in tumor necrosis factor-alpha (TNF) and childhood asthma.
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DOI：
10.1289/ehp.9740
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发表时间：
2007-04
影响因子：
10.4
通讯作者：
London SJ
中科院分区：
文献类型：
--
作者：
Wu H;Romieu I;Sienra-Monge JJ;del Rio-Navarro BE;Anderson DM;Dunn EW;Steiner LL;Lara-Sanchez Idel C;London SJ
促炎细胞因子基因肿瘤坏死因子-α（TNF）和光氧合酶-α（LTA，也称为TNF-β）的多态性在一些研究中与哮喘和特应性相关。父母吸烟是儿童哮喘的一贯危险因素。二手烟和臭氧都能刺激TNF的产生。我们的目标是调查TNF和LTA的遗传变异是否与哮喘和特应性相关，以及这种相关性是否被高臭氧暴露的墨西哥人群中的父母吸烟所改变。我们在墨西哥城的596个核心家庭中，包括4-17岁的哮喘患者及其父母，对TNF和LTA的6个标记单核苷酸多态性（SNP）进行了基因分型，包括功能变异。特应性通过皮肤点刺试验确定。TNF-308 SNP的A等位基因与哮喘风险增加相关[相对风险（RR）= 1.54; 95%可信区间（CI），1.04-2.28]，尤其是在父母不吸烟的儿童中（RR = 2.06; 95% CI，1.19-3.55;相互作用p = 0.09）。同样，TNF-238 SNP的A等位基因与父母不吸烟的儿童哮喘风险增加相关（RR = 2.21; 95%CI，1.14-4.30;相互作用p = 0.01）。LTA SNP与哮喘无关。单倍型分析反映了单个SNP的大小和方向。TNF和LTA SNP与特应性程度无关。我们的研究结果表明，TNF的遗传变异可能有助于儿童哮喘，这种关联可能会被父母吸烟所改变。
Polymorphisms in the proinflammatory cytokine genes tumor necrosis factor-α (TNF) and lymphotoxin-α (LTA, also called TNF-β) have been associated with asthma and atopy in some studies. Parental smoking is a consistent risk factor for childhood asthma. Secondhand smoke and ozone both stimulate TNF production. Our goal was to investigate whether genetic variation in TNF and LTA is associated with asthma and atopy and whether the association is modified by parental smoking in a Mexican population with high ozone exposure. We genotyped six tagging single nucleotide polymorphisms (SNPs) in TNF and LTA, including functional variants, in 596 nuclear families consisting of asthmatics 4–17 years of age and their parents in Mexico City. Atopy was determined by skin prick tests. The A allele of the TNF-308 SNP was associated with increased risk of asthma [relative risk (RR) = 1.54; 95% confidence interval (CI), 1.04–2.28], especially among children of non-smoking parents (RR = 2.06; 95% CI, 1.19–3.55; p for interaction = 0.09). Similarly, the A allele of the TNF-238 SNP was associated with increased asthma risk among children of nonsmoking parents (RR = 2.21; 95% CI, 1.14–4.30; p for interaction = 0.01). LTA SNPs were not associated with asthma. Haplotype analyses reflected the single SNP findings in magnitude and direction. TNF and LTA SNPs were not associated with the degree of atopy. Our results suggest that genetic variation in TNF may contribute to childhood asthma and that associations may be modified by parental smoking.
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影响因子：
5.2
作者：
Horvath, S;Xu, X;Laird, NM
通讯作者：
Laird, NM
DOI：
10.1165/ajrcmb.10.5.8179909
发表时间：
1994-05-01
影响因子：
6.4
作者：
BRADDING, P;ROBERTS, JA;HOLGATE, ST
通讯作者：
HOLGATE, ST
DOI：
10.1164/rccm.200305-684oc
发表时间：
2003-11-15
影响因子：
24.7
作者：
David, GL;Romieu, I;London, SJ
通讯作者：
London, SJ
影响因子：
14.2
作者：
Colilla, S;Nicolae, D;Cox, NJ
通讯作者：
Cox, NJ
影响因子：
2.7
作者：
Di Somma, C;Charron, D;Ruffilli, A
通讯作者：
Ruffilli, A