TNF-α+489基因多态性与慢性阻塞性肺疾病急性加重表型的相关性研究  

Relationship between gene polymorphisms of tumor necrosis factor-α+489 and phenotype of acute exacerbation chronic obstructive pulmonary diseases

作　　者：余苏云[1] 高习文[1] 颜志军[1] 李艳[1] YU Su-yun;GAO Xi-wen;FAN Zhi-jun;LI Fan(Department of Respiratory Medicine,Minhang Hospital Affiliated to Fudan University,Shanghai 201199,China)

机构地区：[1]复旦大学附属闵行医院上海市闵行区中心医院呼吸内科,上海201199

出　　处：《临床肺科杂志》2018年第8期1405-1409,共5页Journal of Clinical Pulmonary Medicine

基　　金：上海市卫生局青年科研项目(No 20134y084)

摘　　要：目的分析肿瘤坏死因子-α+489(tumor necrosis factor-α+489,TNF-α+489)GA基因型的异质性与患者慢性阻塞性肺疾病急性加重(acute exacerbation chronic obstructive pulmonary diseases,AECOPD)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AECOPD患者作为AECOPD组,其中男160例,女38例,年龄57-94岁,平均(79.76±8.56)岁。同期纳入195名健康体检者为对照组,其中男159例,女36例,年龄52-89岁,平均(81.26±9.29)岁。采用测序法检测两组外周血中TNF-α+489基因型分布情况,进而比较不同基因型在AECOPD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+489可检出GG型、GA型及AA型3种基因型,AECOPD组3种基因型发生率分别为70.71%、23.23%和6.06%,而对照组分别为75.90%、20.00%和4.10%,组间比较差异无统计学意义(P>0.05)。两组中等位基因G/A出现频率比较,AECOPD组中G%为82.32%,A%为17.68%;而健康人群组中G%为85.90%,A%为14.10%,组间比较差异无统计学意义(P>0.05)。AECOPD组中AA型和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与后者比较差异有统计学意义。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(0.26±0.13)cm,GG型为(0.21±0.09)cm;支气管壁的厚度与相邻肺动脉的比值相比,GA/AA型的人群为(0.32±0.13),而GG型人群为(0.28±0.12,P=0.019),差异有统计学意义。结论本组患者中TNF-α+489 GA基因型与AECOPD的易感性无关,但与AECOPD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。Objective To observe the relationship between gene polymorphisms of tumor necrosis factor-α（ TNF-α） ＋ 489 and phenotype of acute exacerbation chronic obstructive pulmonary diseases（ AECOPD）. Methods198 AECOPD cases in Minhang Hospital of Shanghai were recruited into the study group,including 160 male and38 female,aging from 57 to 94 years old,with an average of 79. 76 ± 8. 56. 195 healthy people were recruited into the control group,including 159 male and 36 female,aging from 52 to 89 years old,with an average of 81. 26 ±9. 29. PCR and sequencing method were used to detect the polymorphism of TNF-α ＋ 489 in both groups. Results GG,GA and AA genotypes were detected in the two groups. The frequencies of GG/GA/AA genotype in the AECOPD group were 70. 71%,23. 23% and 6. 06% respectively,and 75. 90%,20. 00% and 4. 10% in the control group. The differences of the genotype between the AECOPD group and the control group were not statistically significant（ P〉0. 05）. The frequencies of G and A were 82. 32% and 17. 68% in the AECOPD group,and 85. 90% and14. 10% in the control group（ P〉0. 05）. Dyspnea,smoke index and the increased thickness of bronchial wall in iconography were the chief clinlcal symptoms in the patients with the TNF-α ＋ 489 genotype of GA/AA. Conclusion There is correlation between genetic predisposition of AECOPD and TNF-α ＋ 489 genotype of GA/AA. Clinical dyspnea,smoke index and the increased thickness of bronchial wall are the chief clinlcal symptoms in the patients with genotype of GA/AA.

关 键 词：TNF-α+489 COPD急性发作 基因表型 

分 类 号：R563.9[医药卫生—呼吸系统]