TLR4基因多态性与中国汉族儿童结核病易感性的关联研究  

Association between polymorphisms of Toll like receptor 4 and susceptibility to tuberculosis in Han Chinese children

作　　者：李洁琼[1] 谢兰品[2] 董雅坤[2] 綦辉[1] 孙琳[1] 焦伟伟[1] 肖婧[1] 徐放[1] 申晨[1] 申阿东[1] 

机构地区：[1]首都医科大学附属北京儿童医院,北京市儿科研究所,儿科学国家重点学科,省部共建儿科重大疾病研究重点实验室,儿童呼吸道感染性疾病研究北京市重点实验室,北京100045 [2]河北省胸科医院,河北省医学重点发展学科

出　　处：《山西医科大学学报》2014年第12期1151-1158,共8页Journal of Shanxi Medical University

基　　金：北京市自然科学基金重点项目(7121007);北京市科技新星计划基金资助项目(2011082)

摘　　要：目的探讨TLR4的基因多态性与中国汉族儿童结核易感性的关系。方法收集348名汉族儿童结核病患者,并按照发病部位和严重程度分为肺内结核病、肺外结核病、重症结核病和非重症结核病亚组,以同期查体的389名儿童作为对照,采用病例对照研究,应用高通量Mass ARRAY技术对于TLR4基因的SNP位点进行基因分型研究。结果研究显示结核组和对照组TLR4基因rs1399431位点基因频率存在差异;rs1399431、rs1927907和rs11536889的基因型频率在亚组间的分布差异具有统计学意义。在显性模式下,rs1927907的A等位基因和rs1399431的T等位基因和正常组比较对于肺外结核病(Prs1927907=0.042和Prs1399431=0.012)具有保护作用;而rs1399431的T等位基因和非重症结核病比较,对于重症TB(Prs1399431=0.012)具有保护作用;在隐性遗传模式下rs11536889的C等位基因和正常组比较对于重症结核病(Prs1399431=0.024)具有易感作用。结论结果提示TLR4基因在结核病易感性方面,特别是结核病亚组之间具有一定作用。Objective To explore the association between gene polymorphisms of Toll like receptor 4（TLR4）and susceptibility to tuberculosis（TB）in Han Chinese children.Methods A case-control study was performed in 348 TB patients（including pulmonary TB,extrapulmonary TB,severe TB and non-severe TB） and 389 healthy controls,who were of Han ethnicity and aged from 0.2 to 18 years.MassARRAY was then used for SNP genotyping.Results The genotype frequency of rs1399431 in TLR4 gene was significantly different between TB group and control group.The genotype frequencies of rs1399431,rs1927907 and rs11536889 in TLR4 gene were also significantly different among pulmonary TB,extrapulmonary TB,severe TB and non-severe TB.Furthermore,rs1927907-A and rs1399431-T of TLR4 gene were found to be associated with reduced risk of developing extrapulmonary tuberculosis （EPTB） （Prs1927907 =0.042 and Ps1399431 =0.012）and severe TB（Prst399431 =0.012） in dominant inheritance model,and rs1399431-T was also associated with reduced risk of severe TB （Prs399431 =0.012）.Similarly,rs11536889-C was associated with risk of severe TB （Prs1399431 =0.024） in recessive inheritance model.Conclusion SNPs of TLR4 gene may be associated with TB,especially EPTB or severe TB in Han Chinese children.

关 键 词：TLR4 多态性 结核病 汉族 儿童 易感性 

分 类 号：R52[医药卫生—内科学]