摘要目的 探讨解整合素金属蛋白酶33(ADAM33)基因V4、T2位点多态性与儿童哮喘易感性及严重程度的相关性.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,四位点用聚合酶链反应-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 哮喘组V4位点C、T2位点A等位基因频率均高于对照组(P ＜0.01,OR =2.36 ～2.96,95％ CI:1.56-1.78 ～3.56-4.94).轻中度和重度哮喘组中V4位点GC基因型频率均高于对照组(P＜0.05),重度哮喘组CC基因型频率高于对照组(P＜0.05)；T2位点GA基因型在重度哮喘组中分布高于对照组(P＜0.01),轻中度哮喘组AA基因型频率高于对照组(P＜0.05)；MDR交互作用分析显示,ADAM33基因V4、T2位点构成最佳模型.结论 ADAM33基因V4、T2位点与儿童哮喘发生及其严重程度相关,同时ADAM33基因V4、T2位点均具有明显交互作用.

abstractsObjective To verify the association of a disintegrin and metalloproteinase domain 33 (ADAM33) polymorphisms in childhood asthma susceptibility and severity in patients with moderate and severe asthma.Methods A total of 144 controls and 110 asthmatic patients were recruited for this hospitalbased case-control study.Two polymorphic sites (V4,T2) were genotyped using the polymerase chain reaction-restriction fragment length polymorphism method.The gene-gene interactions were analyzed with the multifactor dimensionality reduction (MDR) software.Results The allele frequencies of three SNPs (V4,T2) of ADAM33 in childhood asthma group were significantly higher than control group (P ＜ 0.01,OR =2.36 ～ 2.96,95％ CI:1.56-1.78 ～ 3.56-4.94).For the SNPs V4,GC genotype frequencies of both moderate and severe groups were significantly higher from the control group (P ＜ 0.05) ; the CC genotype frequencies in severe group were significantly higher than control group (P ＜ 0.05) ; the genotype GA of T2 locus in severe group and AA genotype frequencies in moderate group were significantly higher than control group (P ＜0.01 ～0.05) ; there were no significant differences for both allele and genotype frequencies of S2 locus between the childhood asthma and control group (P ＞ 0.05).By MDR analysis,the best interaction model was the four-factor model that the V4,T2 genotypes were the subgroup to predict asthma risk.Conclusions Our results highlight the role of ADAM33 as a susceptibility gene for childhood asthma,and the interactions among ADAM33 V4 and T2 are also associated with childhood asthma.