ADAM33基因V4、T2位点基因多态性与哮喘相关性研究

Association of polymorphism of V4 and T2 locus alleles in ADAM33 gene with asthma susceptibility

目的探讨解整合素金属蛋白酶33（ADAM33）基因v4、他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）；12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、他位点构成最佳模型。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。

Objective 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 hospital- based case-control study. Two polymorphic sites （V4,T2） were genotyped using the polymerase chain reac- tion-restriction fragment length polymorphism method. The gene-gene interactions were analyzed with the muhifactor 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 con- trol group （ P 〈 0. 01 - 0. 05） ; there were no significant differences for both allele and genotype frequen- cies of $2 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.