TLR4基因启动子区多态性及其对蛋白表达的影响  

Single Nucleotide Polymorphism in TLR4 Promoter and its Effect on Protein Expression

作　　者：王永堂[1] 蒋建新[1] 段朝霞[1] 顾玮[1] 曾灵[1] 陈客宏[1] 

机构地区：[1]第三军医大学大坪医院野战外科研究所烧伤与复合伤国家重点实验室,重庆400042

出　　处：《现代生物医学进展》2009年第7期1209-1212,F0003,共5页Progress in Modern Biomedicine

基　　金：国家重点基础研究发展规划项目("973"项目)(2005CB522602);国家杰出青年科学基金项目(30325040)

摘　　要：目的:检测中国人群Toll样受体4(Toll-like receptor4,TLR4)基因5'调控区的单核苷酸多态性(single nucleotide polymorphisms,SNPs),探讨其与TLR4蛋白表达的关系。方法:采用聚合酶链反应-限制性片段长度多态性法(PCR-RFLP)对正常汉族人群样本TLR4启动子区-2242、-1892和-1837这3个可能有意义的SNP位点进行基因分型,以确定中国人群中TLR4基因启动子区SNP基因型和发生频率。取其中89例全血标本用全血培养模型检测内毒素刺激前后TLR4蛋白的表达变化,进一步探讨TLR4启动子区单核苷酸多态性对其蛋白表达的影响。结果:TLR4启动子区-2242、-1892和-1837这3个可能有意义的SNP位点等位基因频率分别是43.27%、27.70%和42.75%。TLR4蛋白表达检测结果表明内毒素刺激后-2242位点TC与CC基因型TLR4蛋白的表达显著高于TT基因型(P<0.05),其它位点则没有影响。结论:中国汉族人群中TLR4基因启动子区-2242位点可能是脓毒症关联分析重要的遗传标记。Objective：To identify the single nucleotide polymorphisms （SNPs） in the 5′ regulatory region of human Toll-like receptor 4 （TLR4） gene and to study its effects on the expression of TLR4 protein in Chinese. Methods：The -2242, -1892 and -1837 polymorphic sites in 5′ flank region of TLR4 gene identified before were analyzed in Chinese population by using polymerase chain reaction （PCR） -restriction fragment length polymorphism （RFLP） method. To figure out the fimction of the SNPs, we further investigated the TLR4 protein levels in 89 whole blood samples with/without lipopolysaccharide （LPS） treatment fi＇om healthy person. Results：In the samples of Han population from Chongqing, the minor allele frequencies of-2242, -1892 and -1837 SNPs were 43.27%, 27.70% and 42.75%, separately. Further investigation of the TLR4 protein indicated that the TLR4 expression in leukocytes was higher in heterozyous TC and homozygous CC than in homozygous TT （P〈0.05） after LPS stimulation in -2242 SNP, while no change was observed in -1892 and -1837 SNPs. Conclusion：Sampling analysis in Han population of Chongqing showed that the -2242 polymorphism of TLR4 may be an important functional variant in Chinese Han population, which might be used as a relevant genetic maker for sepsis in trauma patients.

关 键 词：TLR4 脂多糖 单核苷酸多态性 脓毒症 

分 类 号：R394-33[医药卫生—医学遗传学] R394.3[医药卫生—基础医学]