TGF-β1和ADAM33基因交互作用与儿童哮喘易感性及严重程度相关性

Association of the interactions between TGF-β1 and ADAM33 gene with susceptibility and severity in childhood asthma

目的:探讨转化生长因子β1(TGF-β1)和解整合素金属蛋白酶33(ADAM33)基因单核苷酸多态性与儿童哮喘易感性及严重程度相关性。方法:采用以医院为基础的病例对照研究(110例哮喘患儿和144例对照)方法,三个多态性位点(V4、T2、T869C)用聚合酶链反应-限制性片段长度多态性分析(PCR-RFLP)技术进行基因分型,应用MDR软件分析基因各位点之间交互作用。结果:TGF-β1基因的T869C位点基因型及等位基因频率分布在哮喘组和对照组比较差异均无统计学意义(P>0.05)。哮喘组ADAM33基因V4位点C和T2位点A等位基因频率显著高于对照组(P<0.01),而V4位点的CC基因型及T2位点的GA基因型分布在轻中度哮喘组与对照组比较差异无统计学意义(P>0.05),T2位点的AA基因型分布在重度哮喘与对照组比较无显著性差异(P>0.05)。MDR交互作用分析显示,ADAM33基因V4和T2位点构成的2个位点最佳模型;ADAM33基因位点V4、T2和TGF-β1位点T869C构成的3个位点最佳模型两组比较均有统计学差异(P<0.05)。结论:ADAM33基因V4和T2位点与儿童哮喘发生及其严重程度相关。

Objective：To verify the association of transforming growth factor-β1 and a disintegrin and metalloproteinase domain 33 polymorphisms with childhood asthma susceptibility and severity in a sample of patients with moderate and severe asthma. Methods：A total of 144 controls and 110 asthmatic patients were recruited for this hospital-based case-control study. Three polymorphic sites （T869C, V4 ,T2）were genotyped using the polymerase chain reaction-restriction fragment length polymorphism method. The gene-gene interactions were analyzed with the MDR software. Results：There were no significant differences for both allele and genotype frequencies of T869C of TGF-β1 gene between the childhood asthma and control group （ P 〉 0.05 ）. The allele frequencies of two SNPs （ V4, T2） of ADAM33 in childhood asthma group was significantly higher than that in control group （P 〈 0.01 ）. The nonsignificant differences were observed for the genotype CC of V4 locus and the genotype GA of T1 locus between moderate asthmatic groups and controls （ P = 0. 129 and 0. 084, respectively）, the genotype AA of T2 locus was no statistical significance between severe asthma and controls （P = 0.063 ）. There were significant differences in the interaction model between TGF-β1 and ADAM33 gene （including 2 and 3 loci best model） analyzed by MDR （P 〈 0.05 ）. Conclusion： The results highlight the role of ADAM33 as a susceptibility gene for children asthma, and the interactions among TGF-β1 T869C and ADAM33 V4 and T2 also have associations with children asthma in Chinese Han people.