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Toll样受体5基因多态性与中国人群脓毒症的相关性研究
引用本文:王志富,;周钢桥,;方宇,;张红星,;智联腾,;张秀梅,;翟芸,;乐伟,;冯凯,;刘保池,;陈惠鹏,;凌焱,;李玉霞,;贺福初. Toll样受体5基因多态性与中国人群脓毒症的相关性研究[J]. 国外医学:分子生物学分册, 2009, 0(4): 325-330
作者姓名:王志富,  周钢桥,  方宇,  张红星,  智联腾,  张秀梅,  翟芸,  乐伟,  冯凯,  刘保池,  陈惠鹏,  凌焱,  李玉霞,  贺福初
作者单位:[1]北京协和医学院基础医学院(中国医学科学院基础医学研究所),北京市100730; [2]军事医学科学院放射与辐射医学研究所(北京蛋白质组研究中心蛋白质组学国家重点实验室),北京市100850; [3]郑州大学第一附属医院急诊科,郑州市450052; [4]中国人民解放军306医院中心实验室,北京市100101; [5]复旦大学附属公共卫生临床中心,上海市201508; [6]军事医学科学院生物工程研究所,北京市100071
基金项目:北京协和医学院基础医学院,中国医学科学院基础医学研究所和军事医学科学院放射与辐射医学研究所对本研究具有相同的贡献.资助项目:国家重点基础研究发展规划项目(973计划)(No.2005CB522602),北京市科技新星计划项目(No.2006A54)
摘    要:目的探讨Toll样受体5(Toll-likereceptor5,TLR5)基因多态性位点与脓毒症发生风险及疾病严重程度的相关性。方法采用病例一对照研究设计,募集了255例脓毒症患者和260例对照个体。应用贝克曼公司的商用SNPstream分型技术和PCR—RFLP方法对TLR5基因的3个编码区多态性位点进行分型。采用Logistic回归分析,校正性别、年龄、吸烟和饮酒、慢性病状态、APACHEⅡ评分和脓毒症病因等混杂因素的影响,评价多态性位点与脓毒症的发生风险,以及脓毒症性休克、死亡和器官功能障碍等表型的遗传相关性。结果TLR5基因的3个多态性位点在病例和对照组中的基因型分布均呈哈.温平衡状态。这3个编码区的多态性位点与脓毒症的发生风险和疾病严重程度均无遗传学关联。结论TLR5基因的多态性位点可能在脓毒症的发生、发展和病程转归中不发挥重要作用。

关 键 词:脓毒症  单核苷酸多态性  Toll样受体5  遗传关联

Irrelevance of Polymorphisms of TLR5 Gene to Sepsis of Chinese Population
Affiliation:WANG Zhifu, ZHOU Gangqiao, FANG Yu, ZHANG Hongxing, ZHI Lianteng, ZHANG Xiumei, ZHAI Yun, YUE Wei, FENG Kai, LIU Baochi, CHEN Huipeng, LING Yan ,LI Yuxia, HE Fuchu( 1School of Basic Medicine, Peking Union Medical College, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, Beijing, 100730, China 2State Key Laboratory of Proteomics , Beijing Proteome Research Center, Belting Institute of Radiation Medicine, Beijing , 100850, China 3Department of Emergency, The First Affiliated Hospital, College of Medicine, Zhengzhou University, Zhengzhou, 450052, China 4Laboratory Center, Chinese PLA 306 Hospital, Beijing, 100101, China;5Shanghai Public Health Clinical Center, Fudan University, Shanghai, 201508, China; 6Department of Microbial Genomics, Beijing Institute of Biotechnology, Beijing, 100071, China)
Abstract:Objective Toll-like receptor 5 (TLR5) is able to recognize bacterial flagellin of both Gram-negative and -positive bacteria, activate NF-KB signal pathway and play a central role in sepsis. In the present study, we investigated whether the polymorphisms of TLR5 gene is associated with susceptibility to and disease severity of sepsis. Methods Three TLR5 polymorphisms, R392X (rs5744168), S592N (rs2072493) and L616F (rs5744174) in exon 6, were genotyped in 255 patients with sepsis and 260 control subjects by the Beckman SNPstream genotyping platform and PCR- RFLP analysis. The associations with susceptibility to and disease severity of sepsis were estimated by logistic regression, with controlling for confounding factors, including age, sex, smoking status, drinking status, chronic diseases status, APACHEII and critical illness status. Result Genotype frequencies of these three polymorphisms were conformed to the Hardy-Weinberg equilibrium in both patients and controls. On the basis of logistic regression analysis with adjustment for confounding factors, no significant association was found between polymorphisms of and susceptibility to sepsis. Also no significant association with septic shock, sepsis caused death and the number of organ dysfunction was found within the three polymorphisms. Conclusion Our findings suggest that the TLR5 polymorphisms R392X, S592N and L616F do not play a major role in mediating susceptibility to and disease severity of sepsis.
Keywords:sepsis  single nucleotide polymorphism  TLR5  genetic association
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