ADAM33基因多态性影响慢性阻塞性肺疾病气道炎症

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。

ADAM33 Gene Polymorphism Is Correlated with Airway Inflammation of COPD

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.