支气管哮喘易感区域5q31-33内Tim-3基因单体型分析

目的： 探讨染色体上支气管哮喘易感区域5q31-33内Tim-3基因多态性与支气管哮喘的关系。方法：应用限制性片段长度多态性技术方法，分析了118个儿童变应性哮喘核心家系Tim-3基因4个SNPs(rs10053538、rs10515746、rs13170556和rs9313441)的基因型；采用基于家系传递不平衡检验（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：①基于家系的TDT分析显示，Tim-3基因的4个SNPs由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，与哮喘无关（P>0.05）。②Transmit多个位点单体型分析结果显示由Tim-3基因rs10053538、 rs13170556、 rs9313441构建的单体型与支气管哮喘有关联（Global 2=10.83，P<0.05）。父母传递给患病子女GGG单体型的观察值小于期望值，差异显著（2=8.24，P<0.01）。结论：中国汉族人群中，位于染色体5q31-33区域的Tim-3基因本身或其附近的基因可能与儿童变应性哮喘的易感性相关。

Haplotype analysis of Tim-3 gene polymorphisms within asthma susceptible region 5q31-33

AIM: To investigate the relationship between Tim-3 gene polymorphisms within chromosome susceptible region 5q31-33 and asthma. METHODS: The genotypes of 4 SNPs (rs10053538, rs10515746, rs13170556 and rs9313441) in 118 allergic asthma nuclear pedigrees were analyzed by restriction fragment length polymorphism. Family-based association analysis method for transmission disequilibrium test (TDT) was employed for the data processing. Haplotypes and their frequencies were established and analyzed by TRANSMIT software. RESULTS: ① No transmission disequilibrium was found in 4 SNPs of Tim-3 from heterozygous parents onto patients in our 118 trios analyzed by TDT (P>0.05). The 4 SNPs were not associated with asthma. ② The family-based haplotype analysis showed that the haplotypes of Tim-3 constructed by rs10053538, rs13170556, rs9313441 were associated with asthma (2=10.83, P<0.05). The observed numbers of haplotype GGG from parents to the affected offsprings were less than the expected numbers, which showed a significant biased transmission (2=8.24，P<0.01). CONCLUSION: The Tim-3 gene in chromosome 5q31-33 itself or a locus nearby may confer susceptibility to asthma in this Chinese Han population.