Castro-Giner F, Kogevinas M, Imboden M, de Cid R, Jarvis D, Mächler M, Berger W, Burney P, Franklin K A, Gonzalez J R, Heinrich J, Janson C, Omenaas E, Pin I, Rochat T, Sunyer J, Wjst M, Antó J-M, Estivill X, Probst-Hensch N M
Centre for Research in Environmental Epidemiology, Municipal Institute of Medical Research (IMIM-Hospitaldel Mar), Barcelona, Spain.
Eur Respir J. 2009 May;33(5):1003-9. doi: 10.1183/09031936.00140608. Epub 2009 Feb 5.
Obesity is a risk factor for asthma. Adipose tissue expresses pro-inflammatory molecules including tumour necrosis factor (TNF), and levels of TNF are also related to polymorphisms in the TNF-alpha (TNFA) gene. The current authors examined the joint effect of obesity and TNFA variability on asthma in adults by combining two population-based studies. The European Community Respiratory Health Survey and the Swiss Cohort Study on Air Pollution and Lung and Heart Disease in Adults used comparable protocols, questionnaires and measures of lung function and atopy. DNA samples from 9,167 participants were genotyped for TNFA -308 and lymphotoxin-alpha (LTA) +252 gene variants. Obesity and TNFA were associated with asthma when mutually adjusting for their independent effects (odds ratio (OR) for obesity 2.4, 95% confidence interval (CI) 1.7-3.2; OR for TNFA -308 polymorphism 1.3, 95% CI 1.1-1.6). The association of obesity with asthma was stronger for subjects carrying the G/A and A/A TNFA -308 genotypes compared with the more common G/G genotype, particularly among nonatopics (OR for G/A and A/A genotypes 6.1, 95% CI 2.5-14.4; OR for G/G genotype 1.7, 95% CI 0.8-3.3). The present findings provide, for the first time, evidence for a complex pattern of interaction between obesity, a pro-inflammatory genetic factor and asthma.
肥胖是哮喘的一个风险因素。脂肪组织会表达包括肿瘤坏死因子（TNF）在内的促炎分子，并且TNF水平也与肿瘤坏死因子-α（TNFA）基因的多态性有关。当前作者通过合并两项基于人群的研究，检验了肥胖和TNFA变异性对成年人哮喘的联合影响。欧洲共同体呼吸健康调查以及瑞士成人空气污染与肺和心脏病队列研究采用了可比的方案、问卷以及肺功能和特应性测量方法。对9167名参与者的DNA样本进行了TNFA -308和淋巴毒素-α（LTA）+252基因变异的基因分型。在相互调整肥胖和TNFA的独立影响后，肥胖和TNFA均与哮喘相关（肥胖的优势比（OR）为2.4，95%置信区间（CI）为1.7 - 3.2；TNFA -308多态性的OR为1.3，95%CI为1.1 - 1.6）。与更常见的G/G基因型相比，携带G/A和A/A TNFA -308基因型的受试者中肥胖与哮喘的关联更强，尤其是在非特应性个体中（G/A和A/A基因型的OR为6.1，95%CI为2.5 - 14.4；G/G基因型的OR为1.7，95%CI为0.8 - 3.3）。本研究结果首次为肥胖、一种促炎遗传因素和哮喘之间复杂的相互作用模式提供了证据。
