TNFA-3086>A in two international population-based cohorts and risk of asthma
TNFA-3086>A in two international population-based cohorts and risk of asthma
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DOI：
10.1183/09031936.00155607
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发表时间：
2008-08-01
影响因子：
24.3
通讯作者：
Probst-Hensch, N. M.
中科院分区：
文献类型：
--
作者：
Castro-Giner, F.;Kogevinas, M.;Probst-Hensch, N. M.
遗传关联研究已将肿瘤坏死因子-a 基因 (TNFA) 的鸟嘌呤至腺嘌呤取代核苷酸 -308 (-3086 > A) 多态性与哮喘风险增加联系起来，但结果不一致。本研究的目的是通过结合两项大型人群多中心研究的结果并对先前发表的研究进行荟萃分析，测试 TNFA 和淋巴毒素-α 基因 (LTA) 的两种单核苷酸多态性是否与成人哮喘、支气管高反应性和特应性相关。欧洲共同体呼吸健康调查 (ECRHS) 和瑞士成人空气污染与肺病和心脏病队列研究 (SAPALDIA) 使用了类似的方案，包括呼吸道症状调查问卷以及肺功能和特应性测量。来自 11,136 名参与者的 DNA 样本在 TNFA -308 和 LTA 252 上进行了基因分型。使用了采用固定和随机效应模型以及非参数技术的逻辑回归。哮喘患病率为6%。 TNFA -3086 > A 多态性与哮喘患病率增加和支气管高反应性相关。没有发现与特应性的一致关联。 LTA 252A > G 多态性与任何结果均不相关。对 17 项研究的荟萃分析显示，TNFA -308 腺嘌呤等位基因会增加哮喘风险。肿瘤坏死因子-α基因核苷酸-308多态性与哮喘和支气管高反应性风险中度增加相关，但与特应性无关。这些结果得到了先前发表的研究的荟萃分析的支持。
Genetic association studies have related the tumour necrosis factor-a gene (TNFA) guanine to adenine substitution of nucleotide -308 (-3086 > A) polymorphism to increased risk of asthma, but results are inconsistent. The aim of the present study was to test whether two single-nucleotide polymorphisms, of TNFA and of the lymphotoxin-alpha gene (LTA), are associated with asthma, bronchial hyperresponsiveness and atopy in adults, by combining the results of two large population-based multicentric studies and conducting a meta-analysis of previously published studies. The European Community Respiratory Health Survey (ECRHS) and Swiss Cohort Study on Air Pollution and Lung and Heart Diseases in Adults (SAPALDIA) used comparable protocols, including questionnaires for respiratory symptoms and measures of lung function and atopy. DNA samples from 11,136 participants were genotyped at TNFA -308 and LTA 252. Logistic regression employing fixed and random effects models and nonparametric techniques were used. The prevalence of asthma was 6%. The TNFA -3086 > A polymorphism was associated with increased asthma prevalence and with bronchial hyperresponsiveness. No consistent association was found for atopy. The LTA 252A > G polymorphism was not associated with any of the outcomes. A meta-analysis of 17 studies showed an increased asthma risk for the TNFA -308 adenine allele. The tumour necrosis factor-alpha gene nucleotide -308 polymorphism is associated with a moderately increased risk of asthma and bronchial hyperresponsiveness, but not with atopy. These results are supported by a meta-analysis of previously published studies.