肿瘤坏死因子α-308基因多态性与慢性阻塞性肺疾病易感性的荟萃分析

目的运用荟萃分析方法综合评价肿瘤坏死因子α基因启动子308位（TNF-α-308）G／A基因型与慢性阻塞性肺疾病（COPD）的相关性。方法检索Medline和中国生物医学光盘数据库，获取TNF-α-308基因多态性与COPD易感性的病例一对照研究，使用统一的表格提取资料，应用RevMan 4．2软件进行统计学处理。结果检索的17篇文献中有18个病例-对照研究，共有1606例COPD患者（亚洲人666例，白种人940例）和2551例对照（亚洲人898例，白种人1653例）被纳入荟萃分析。亚洲人群等位基因TNF2与COPD密切相关（OR=2．62，95％CI为2．00～3．43），基因型TNF1／2及基因型TNF1／2合并TNF2／2者的COPD易感性高于基因型TNF1／1者（OR=2．44，95％CI为1．79-3．33及OR=2．78，95％CI为2．06～3．75），校正吸烟前后的敏感性结果相似。白种人等位基因TNF2与COPD易感性无相关性（OR=0．97，95％CI为0．84～1．14），基因型TNF1／2及基因型TNF1／2合并TNF2／2者的COPD易感性与基因型TNF1／1者相似（OR=0．96，95％CI为0．79～1．16及OR=1．03，95％CI为0．86～1．25），校正吸烟前后的敏感性结果相似。结论在亚洲人群中TNF2等位基因是COPD的危险因素，在白种人群中TNF-α-308的G／A基因多态性与COPD易感性无关。

Association of tumor necrosis factor alpha 308 G/A gene promoter polymorphism with the presence of chronic obstructive pulmonary disease:a meta-analysis

OBJECTIVE: To investigate the association between the polymorphism of tumor necrosis factor alpha 308 gene (TNF-alpha-308) promoter and the risk of chronic obstructive pulmonary disease (COPD) using the method of meta-analysis. METHOD: The database of Medline and the Chinese biomedicine disc (CBM) were searched for published case-control studies of the association between the polymorphism of TNF-alpha-308 gene promoter and COPD. Data were extracted using a standardized form and the meta-analysis was performed. RESULTS: Eighteen case-control studies, comprising 1606 patients with COPD and 2551 controls (the oriental population: 666 patients with COPD and 898 controls; the Caucasian: 940 patients with COPD and 1653 controls) were included in the meta-analysis. Using a fixed effect model, the pooled result in the oriental population showed that the TNF2 allele was associated with the susceptibility to COPD [odds ratio (OR) = 2.62, 95% confidence interval (95% CI) 2.00 to 3.43]. The OR for COPD susceptibility in TNF1/2 population was significantly increased at 2.44 (95% CI 1.79 to 3.33) compared to the TNF1/1 population. The OR for COPD susceptibility in the TNF1/2 plus TNF2/2 population was significantly increased at 2.78 (95% CI 2.06 to 3.75) compared to the TNF1/1 population. When adjusted for smoking, the result was similar. However, in the Caucasian population, the TNF2 allele was not associated with the susceptibility to COPD (OR = 0.97, 95% CI 0.84 to 1.14). There was no association between the genotype of TNF-alpha-308 and COPD (OR = 0.96, 95% CI 0.79 to 1.16, and OR = 1.03, 95% CI 0.86 to 1.25), compared between the TNF1/2 population, the TNF1/2 plus the TNF2/2 population and the TNF1/1 population respectively. When adjusted for smoking, the result was similar. CONCLUSION: In the oriental population, the TNF2 allele confers a significant risk for developing COPD. There is no association between the polymorphism of TNF-alpha-308 gene promoter and COPD in the Caucasian population.