摘要目的 分析肿瘤坏死因子-α-308(tumor necrosis factor-α-308,TNF-α-308)GA基因型的异质性与患者慢性阻塞性肺疾病(慢阻肺)急性加重表型的相关性.方法 纳入2014年1月至2015年6月复旦大学附属闵行医院呼吸科收住院的198例慢阻肺急性加重患者作为慢阻肺急性加重组,其中男160例,女38例,年龄57～94岁,平均(80±9)岁.同期纳入195名健康体检者为对照组,其中男159名,女36名,年龄52 ～ 89岁,平均(81±9)岁.采用测序法检测两组外周血中TNF-α-308基因型分布情况,进而比较不同基因型在慢阻肺急性加重人群中临床表型、急性加重表型及影像学表型方面的差异性.结果 两组对象外周血中TNF-α-308可检出GG、GA及AA型3种基因型,慢阻肺急性加重组3种基因型发生率分别为87.4％、10.6％和2.0％,而对照组分别为95.4％、4.6％和0,组间比较差异有统计学意义(P＜0.05).两组中等位基因G/A出现频率比较,慢阻肺急性加重组中G％为92.7％,A％为7.3％;而健康人群组中G％为97.7％,A％为2.3％,组间比较差异有统计学意义(P＜0.05).慢阻肺急性加重组中AA和GA型的患者与单纯GG型的患者比较,前者频繁急性加重的比例较后者增多.GA/AA型的患者主要临床表现为呼吸困难,而GG型患者主要表现为咳嗽、咳痰,GA/AA型患者的吸烟指数明显高于GG型.影像学方面,GA/AA型的患者支气管壁的厚度增加更明显(0.27±0.13) mm,GG型为(0.17±0.04) mm;支气管壁的厚度与相邻肺动脉的比值在GA/AA型患者中为0.38±0.14,而GG型为0.28±0.11(P ＜0.05),差异有统计学意义.结论 本组患者中TNF-α-308 GA基因型与慢阻肺急性加重的易感性相关,且与慢阻肺急性加重的频繁急性加重相关,临床上表现为呼吸困难为主,吸烟指数更高,影像学上表现为支气管壁的厚度增加明显.

abstractsObjective To observe the relationship between gene polymorphisms of tumor necrosis factor-α (TNF-α)-308 and phenotypes of acute exacerbation of chronic obstructive pulmonary diseases (AECOPD).Methods 198 AECOPD cases in the Minhang Hospital of Shanghai were recruited into the patient group,and 195 healthy people were recruited into the control group.PCR and sequencing method were used to detect the polymorphism of TNF-o-308 in all the people.Results Three genotypes with GG,GA and AA were detected in the 2 groups.The frequencies of GG/GA/AA genotype in AECOPD group were 87.4％,10.6％ and 2.0％ respectively,and the control group were 95.4％,4.6％ and 0 respectively.The differences of the genotypes between AECOPD and health control were statistically significant (P ＜ 0.05).The frequencies of G and A were 92.7％ and 7.3％ in the AECOPD group,97.7％ and 2.3％ in the control group.The differences were statistically significant (P ＜ 0.05).Dyspnea,smoke index and the increased thickness of bronchial wall in lung HRCT were the clinical features in patients with the TNF-α-308genotype of GA/AA.Conclusion There is correlation between genetic predisposition of AECOPD and TNF-α-308 genotype of GA/AA.Clinical dyspnea,smoke index and increased thickness of bronchial wall are the chief clinical features in patients with genotype of GA/AA.