毒性T细胞抗原4功能性遗传多态与儿童哮喘发病风险的关系

目的毒性T细胞抗原4（cytotoxic T-lymphocyte antigen-4,CTLA-4）是细胞免疫调控过程中的关键因子,在哮喘发病过程中起重要作用。本研究探讨CTLA-4编码区遗传多态＋49 G〉A单核苷酸多态与深圳地区儿童哮喘遗传易感性的关系。方法以聚合酶链反应（PCR）和限制性片段长度多态性（restriction fragment length polymorphism,RFLP）分析方法,检测了118例哮喘患儿和160例正常对照者CTLA-4＋49 G〉A基因型,比较不同基因型与哮喘发病风险的关系。结果 CTLA-4＋49 A等位基因频率在哮喘患儿和正常对照中的分布有显著性差异（32.6%vs 24.7%,P=0.039）。CTLA-4三种基因型GG、GA和AA在病例和对照组中的分布有统计学显著性差异（P=0.031,趋势检验）,携带CTLA-4 AA或GA基因型者罹患哮喘的风险是GG基因型携带者的1.62倍（95%CI,0.95-2.68,P=0.05）。结论 CTLA-4单核苷酸多态＋49 G〉A可能是我国儿童哮喘的遗传易感因素。

The relationship of Cytotoxic T-lymphocyte antigen-4 functional genetic polymorphism and the risk for the occurrence of children asthma

Objective：Cytotoxic T-lymphocyte antigen-4（CTLA-4） plays an important role in the regulation of immune system.The ＋49 GA polymorphism in the CTLA-4 leading sequence causing Ala to Thr amino acid substitution in the 17 codon of CTLA-4 was reported to be associated with several allergic diseases.This case-control study was designed to detect the contribution of this polymorphism to susceptibility of asthma in Shenzhen region.Methods：Genotypes were determined in 118 patients with asthma and 160 normal controls.The odds ratios（ORs） and 95% confidence intervals（CIs） were calculated using logistic regression model.Results：We found that the frequency of the ＋49 A allele was significantly higher in cases than in controls（32.6% vs 24.7%,P= 0.04）.The difference among distribution of three genotypes GG,GA and AA was statistically significant between cases and controls（P= 0.031,trend test）.Subjects with the AA or GA genotypes had an increased risk for the occurrence of asthma compared with those with the GG carriers.Conclusion：These findings suggest that CTLA-4 ＋49 GA polymorphism may be a genetic susceptibility factor for asthma in this Chinese population.