Liu Qiji, Shang Linshan, Li Jisheng, Wang Pin, Li Huaichen, Wei Chunhua, Gong Yaoqin
Key Laboratory of Experimental Teratology, Ministry of Education, China, Institute of Medical Genetics, School of Medicine, Shandong University, Jinan, PR China.
Int Arch Allergy Immunol. 2007;144(3):197-202. doi: 10.1159/000103992. Epub 2007 Jun 15.
TIM-1, a member of the T cell immunoglobulin and mucin domain (TIM) gene family was implicated as an asthma susceptibility gene in previous studies. TIM-1 is selectively expressed on activated CD4+ T cells and its expression is sustained preferentially on T helper type 2 (Th2) cells, which suggests that TIM-1 is associated with T cell differentiation and the development of Th2-biased immune response.
In order to evaluate the effects of the promoter polymorphism in the TIM-1 gene on asthma susceptibility in a Chinese Han population, 2 promoter polymorphisms, -416G>C and -1454G>A, from 2 alternative promoter regions, were genotyped in 409 unrelated asthma patients and 305 healthy controls by using polymerase chain reaction and restriction fragment length polymorphism. Also, we analyzed the functional significance of -416G>C using the luciferase reporter gene assay.
We found that -416G>C was associated with asthma susceptibility in our study population (chi2 = 9.88, p = 0.002, odds ratio 1.41, 95% confidence interval 1.14-1.75). No statistically significant difference in the distribution of genotype and allele frequency of the -1454G>A site was observed. The -416G>C substitution increased the transcriptional activity of the TIM-1 gene.
Our findings suggest that the -416G>C variation site in the human TIM-1 promoter region is associated with asthma susceptibility in a Chinese Han population.
T细胞免疫球蛋白和粘蛋白结构域（TIM）基因家族成员TIM-1在先前的研究中被认为是哮喘易感基因。TIM-1在活化的CD4+T细胞上选择性表达，并且其表达优先在2型辅助性T（Th2）细胞上持续存在，这表明TIM-1与T细胞分化及Th2偏向性免疫反应的发展相关。
为了评估TIM-1基因启动子多态性对中国汉族人群哮喘易感性的影响，通过聚合酶链反应和限制性片段长度多态性对来自2个替代启动子区域的2个启动子多态性位点-416G>C和-1454G>A在409例无亲缘关系的哮喘患者和305例健康对照中进行基因分型。此外，我们使用荧光素酶报告基因测定法分析了-416G>C的功能意义。
我们发现在我们的研究人群中-416G>C与哮喘易感性相关（χ2 = 9.88，p = 0.002，比值比1.41，95%置信区间1.14 - 1.75）。在-1454G>A位点的基因型和等位基因频率分布上未观察到统计学上的显著差异。-416G>C替换增加了TIM-1基因的转录活性。
我们的研究结果表明，人类TIM-1启动子区域中的-416G>C变异位点与中国汉族人群的哮喘易感性相关。
