基于家系的Tim-3基因多态性与儿童变应性哮喘的关联研究

Family-based association study of Tim-3 gene 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5q33．2区Tim-3基因启动子两个多态性位点rs10053538和rs10515746与中国湖北地区汉族儿童变应性哮喘的关系。方法应用限制性片段长度多态性技术结合测序方法，分析了118个儿童变应性哮喘核心家系Tim-3基因rs10053538和rs10515746的基因型；采用基于家系的关联分析方法，包括单体型相对风险分析（HRR）和传递不平衡检验（TDT），分析基因分型数据；应用Transmit软件构建单体型并进行单体型关联分析。结果118个核心家庭HRR分析显示Tim-3基因启动子区两个多态性位点rs10053538和rs10515746不使病人具有更高的发病风险（X^2=2．430，P〉0．05；）（X^2=1．368，P〉0．05）。118个满足经典TDT分析的核心家庭中，杂合子父母传递给患病子代的等位基因频率不比预期值高（X^2=2．042，P〉0．05；X^2=0．750，P〉0．05）。Transmit双位点单体型分析也未见父母传递给子女各个单体型的观察值和期望值有明显差异（P〉0．05）。结论中国湖北地区汉族人群中，Tim-3基因启动子区两个多态性位点rs10053538和rs10515746与儿童变应性哮喘不具有相关性。

Objective To investigate the association between two single nucleotide polymorphisms （SNP） rs10053538 and rs10515746 in Tim-3 （T cell immunoglobulin domain and mucin domain protein 3） gene promoter region and child allergic asthma in Chinese Han population from Hubei province by using family-based association study. Methods Genotypes of 2 SNPs （rs10053538 and rs10515746） within Tim-3 gene in 118 allergic asthma nuclear pedigrees were analyzed by restriction fragment length polymorphism and DNA sequencing. Two family-based designs, transmission disequilibrium test （TDT） and haplotype-based haplotype relative risk （HRR） were employed for the data analysis. Haplotypes and their frequencies in 118 nuclear pedigrees were established and analyzed by Transmit software. Results The HRR analysis showed no increased risks of contracting the disease owing to rs10053538 and rs10515746 polymorphisms of Tim-3 promoter in our 118 trios （X^2=2.430, P〉 0.05 ; X^2=1.368,P〉0.05）. No transmission disequilibrium was found from heterozygous parents onto patients in our 118 trios analyzed by TDT（X^2=2.042, P〉0.05;X^2=0.750, P〉0.05 ）. The haplotype analysis also showed no biased transmission of rs10053538 and rs10515746 haplotypes from parents to the affected offsprings（P 〉 0.05）. Conclusion The two SNPs rs10053538 and rs10515746 in Tim-3 gene promoter region are not associated with susceptibility to child allergic asthma in Chinese Han poulation from Hubei orovinee.