基于家系的Tim-1基因启动子多态性与儿童过敏性哮喘的关联研究

Study on the family-based association Tim-1 promoter polymorphism with child allergic asthma

目的:以家系资料为基础,利用遗传不平衡原理探讨染色体5q31-33区Tim-1基因启动子3多态性-2562G>A、-416C>G和-232G>A与湖北地区汉族儿童过敏性哮喘的关系。方法:应用限制性片段长度多态性技术分析了118个儿童过敏性哮喘核心家系Tim-1基因-2562G>A、-416C>G和-232G>A多态性位点的基因型;采用基于家系的传递不平衡检验(TDT)分析基因分型数据;应用TRANSMIT软件构建单倍型并进行单体型关联分析。结果:①118个核心家庭TDT分析显示-2562G>A、-232G>A位点由杂合子父母传递给患病子代的等位基因频率没有偏离50%,差异无显著性(P>0.05),-416C>G位点由杂合子父母传递给患病子代的G等位位点的观察值明显高于期望值(P<0.05)。②TRANSMIT单体型传递不平衡分析显示父母传递给患病子女GCA和GGA单体型的观察值与期望值差异有显著性(P<0.05);Globalχ2检验结果显示Tim-1的单体型与儿童过敏性哮喘有关联(χ2=17.26,P<0.01)。结论:Tim-1基因启动子的-416C>G位点与中国湖北地区汉族儿童过敏性哮喘易感性相关,由其构建的单体型也与哮喘相关。Tim-1基因遗传多态性可能在哮喘的发病中起重要的作用。

Objective：To investigate the association between three single nucleotide polymorphisms-2562GA,-416CG and-232GA in Tim-3（T cell immunoglobulin domain and mucin domain protein 3） gene promoter region and child allergic asthma in Chinese Han population by using family-based association study.Methods：Genotypes of 3 SNPs（-2562GA,-416CG and-232GA） in 118 allergic asthma nuclear pedigrees were analyzed by restriction fragment length polymorphism.The genotype data were analyzed by using the family-based transmission disequilibrium test（TDT）.Haplotypes and their frequencies were established and analyzed by TRANSMIT software.Results：①No transmission disequilibrium was found at the-2562GA and-232GA sites from heterozygous parents onto patients in 118 trios analyzed by TDT（P0.05）;However,at the-416 CG locus,the observed values of G allele from heterozygous parents to offspring were significantly higher than the expected values（P0.05） ②The haplotype TDT analysis by TRANSMIT showed the observed and the expected value in GCA and GGA haplotype from parents to the affected offsprings had significant difference respectively（P0.05）.The Global χ2 test results also showed that Tim-1 haplotype were associated with child allergic asthma （χ2=17.26,P0.01）.Conclusion：Tim-1 gene promoter-416CG locus are associated with allergic asthma susceptibility in Hubei Chinese Han population and the haplotypes constructed by-416CG are also associated with asthma.Tim-1 genetic polymorphism may play an important role in the pathogenesis of asthma.