ADAM33基因多态性影响慢性阻塞性肺疾病气道炎症

ADAM33 Gene Polymorphism Is Correlated with Airway Inflammation of COPD

目的探讨解整连蛋白和金属蛋白33(ADAM33)基因多态性与COPD气道炎症的关系。方法利用引物序列特异性聚合酶链反应-限制性片段长度多态性(PCR-RFLP)的方法检测312例COPD患者4个位点(T2、T1、S2、Q-1)的基因型。同时检测患者诱导痰中细胞数及分类,以及肿瘤坏死因子α(TNF-α)、白细胞介素6(IL-6)、IL-8、血管内皮生长因子(VEGF)的含量,采用t检验分析基因型与炎症反应的关系。结果 T2位点GG基因型携带者较AA和AG基因型携带者诱导痰内细胞总数及TNF-α含量明显升高(P<0.01和P<0.05)。T1位点GG基因型携带者较AA和AG基因型携带者诱导痰淋巴细胞数量明显升高(P<0.05),但AA和AG基因型携带者诱导痰中IL-8含量较高(P<0.05)。Q-1位点GG基因型携带者较AA和AG基因型携带者诱导痰中VEGF和IL-8含量明显升高。S2位点GG基因型携带者较CC和CG基因型携带者诱导痰液细胞总数明显升高(P<0.05),前者诱导痰中IL-8含量明显增加(P<0.01)。结论 ADAM33基因多态性可能通过促进气道炎症而参与COPD的病理过程。

Objective To investigate whether ADAM33（A disintegrin and metalloproteinase 33） gene polymorphism has effect on the airway inflammation of COPD.Methods A total of 312 COPD patients were recruited for this study.Four polymorphic loci（T2,T1,S2,and Q-1） of ADAM33 were selected for genotyping by using the polymerase chain reaction-restriction fragment length polymorphism（PCR-RFLP） method.Total and differential cell counts,contents of TNF-α,IL-6,IL-8,and VEGF in induced sputum were detected.The relationship between genotypes and inflammatory reaction was analyzed.Results On locus T2,the cell counts and content of TNF-α in induced sputum increased significantly in the carriers with GG genotype than those with AA and AG genotypes（P〈0.01 and P〈0.05）.On locus T1,the lymphocyte counts in induced sputum increased significantly in the carriers with GG genotype than those with AA and AG genotypes（P〈0.05）;but the content of IL-8 in induced sputum was higher in AA and AG genotypes（P〈0.05）.On locus Q-1,the contents of VEGF and IL-8 in induced sputum increased significantly in the carriers with GG genotype than those with AA and AG genotypes（P〈0.05）.On locus S2,the total cell counts in induced sputum increased significantly in the carriers with GG genotype than those with CC and CG genotypes（P〈0.05）,and the content of IL-8 in induced sputum increased significantly in GG genotype（P〈0.01）.Conclusion These results suggest that ADAM33 polymorphism may participate the pathogenesis of COPD by promoting airway inflammation.