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.
出处
《现代生物医学进展》
CAS
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)
关键词
TLR4
脂多糖
单核苷酸多态性
脓毒症
TLR4
Lipopolysaccharide
Single nucleotide polymorphism
Sepsis
