A functional polymorphism in the TIM-1 gene is associated with asthma in a Chinese Han population
A functional polymorphism in the TIM-1 gene is associated with asthma in a Chinese Han population
复制标题
TIM-1基因的功能多态性与中国汉族人群的哮喘相关
DOI：
10.1159/000103992
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发表时间：
2007-01-01
影响因子：
2.8
通讯作者：
Gong, Yaoqin
中科院分区：
文献类型：
--
作者：
Liu, Qiji;Shang, Linshan;Gong, Yaoqin
背景：TIM-1 是 T 细胞免疫球蛋白和粘蛋白结构域 (TIM) 基因家族的成员，在之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 T (Th2) 细胞上持续，这表明 TIM-1 与 T 细胞分化和 Th2 偏向免疫反应的发展相关。方法：为了评价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，采用聚合酶链式反应和限制性片段长度多态性对409名无关哮喘患者和305名健康对照者的2个替代启动子区域的2个启动子多态性（-416G>C和-1454G>A）进行基因分型。此外，我们使用荧光素酶报告基因测定分析了 -416G > C 的功能意义。结果：我们发现 -416G > C 与我们研究人群的哮喘易感性相关（chi(2) = 9.88，p = 0.002，比值比 1.41，95% 置信区间 1.14-1.75）。 -1454G>A位点的基因型和等位基因频率的分布没有观察到统计学上的显着差异。 -416G > C 取代增加了 TIM-1 基因的转录活性。结论：我们的研究结果表明，人TIM-1启动子区的-416G>C变异位点与中国汉族人群的哮喘易感性相关。
Background: 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. Methods: 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. Results: We found that -416G > C was associated with asthma susceptibility in our study population ( chi(2) = 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. Conclusion: 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.