Toll样受体9基因启动子单核苷酸多态性与儿童变应性哮喘的相关性  

Association of single nucleotide polymorphisms in the promoter region of the TLR9 gene with childhood atopic asthma

作　　者：钱旭波 吴颖[2] 曹淑彦[2] 蔡晓红[3] 俞晨艺[3] 宣妙燕[3] 曹顺顺[3] 李秀翠[3] 

机构地区：[1]浙江省义乌东方医院儿科,322000 [2]浙江省温州医学院附属育英儿童医院科研中心 [3]浙江省温州医学院附属育英儿童医院儿内呼吸科

出　　处：《中华医学遗传学杂志》2011年第2期185-189,共5页Chinese Journal of Medical Genetics

基　　金：浙江省义乌市科技计划项目（08-3-05）;浙江省医学会临床科研基金（2008ZYC26）;温州市科技局项目（Y20080182）

摘　　要：目的 研究Toll样受体9（toll-like receptor 9,TLR9）基因启动子区单核苷酸多态性在浙江汉族儿童中的分布,探讨其与哮喘易感性及其表型之间的相关性.方法 对312例变应性哮喘患儿（哮喘组）和339名健康儿童（对照组）采用DNA直接测序法检测TLR9基因-1486（rs187084）和-1237（rs5743836）单核苷酸多态性;采用ELISA法检测两组不同基因型血清干扰素γ（interferon-γ,IFN-γ）、白细胞介素12（interleukin-12,IL-12）和白细胞介素4（interleukin-4,IL-4）水平;采用化学发光法检测血清总免疫球蛋白E（immunoglobulin E,IgE）水平;采用酶免疫荧光法检测血清变应原特异IgE.结果 （1）哮喘组和对照组均存在-1486位点T→C突变,哮喘组TT、TC和CC 3种基因型的频率分别是3 8.8%、48.4%和12.8%,对照组分别是41.0%、44.3%和14.7%;未发现-1237位点存在多态性.（2）哮喘组和对照组-1486位点各基因型的频率分布差异无统计学意义（P＞0.05）,年龄分层后比较差异也无统计学意义（P＞0.05）.（3）哮喘组-1486位点3种基因型的血清IFN-γ和IL-4水平差异有统计学意义（P＜0.01）,CC基因型的IFN-γ水平较低而IL-4水平较高;对照组2种细胞因子的差异无统计学意义（P＞0.05）.哮喘组和对照组血清IL-12水平在3种基因型间差异均无统计学意义（P＞0.05）.（4）哮喘组-1486位点不同基因型血清总IgE水平差异无统计学意义（P＞0.05）.结论 浙江汉族儿童不存在TLR9基因-1237位点多态性.TLR9基因-1486 C/T位点单核苷酸多态性与浙江汉族儿童哮喘易感性、血清IL-12及总IgE水平无关;-1486 C/T位点多态性与哮喘患儿血清IFN-γ和IL-4水平有关联,CC基因型的IFN-γ水平较低而IL-4水平较高.Objective To investigate the distribution characteristics of the single nucleotide polymorphisms （SNPs） in the promoter region of the toll-like receptor 9 gene （TLR9）in Chinese Han children from Zhejiang province, and their associations with asthma susceptibility and phenotypes. Methods A case-control study was conducted. A total of 312 asthmatic children aged between 1.9 and 11.6 and 339 age matched healthy controls were enrolled in this study from April 2007 to November 2008. The -1486 C/T in rs187084 and -1237 C/T in rs5743836 loci of the TLR9 gene were genotyped by direct DNA sequencing of the PCR products. Serum levels of IFN-γ, IL-12 and IL-4 were detected by enzyme linked immunosorbent assay. Serum levels of total IgE were detected by chemiluminescence, and serum levels of ildren （P〈0.01）. The CC genotype had the lowest levels of serum IFN-γand the highest levels of serum IL-4 among the three genotypes. There were no significant differences in these cytokines among the healthy controls （P〉0.05）. No statistical differences of serum IL-12 were found among the three genotypes in the two groups （P〉0.05）. （4） There were no significant differences of total IgE （log-transformed） among the three genotypes in the asthmatic children （P〉0. 05）. Conclusion The -1237 C/T polymorphism of TLR9 gene was not detected in Chinese Han children in this study. The - 1486 C/T polymorphism was associated with the levels of serum IFN-γ and IL-4 in children with asthma.However, there were no correlations between the -1486C/T polymorphism and serum IL-12 levels, total IgE levels or asthmatic susceptibility.

关 键 词：儿童哮喘 单核苷酸多态性 Toll样受体9基因 干扰素Γ 白细胞介素12 白细胞介素4 

分 类 号：R725.6[医药卫生—儿科]