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髓样分化因子88基因多态性与脓毒症易感性及严重程度的关联研究 被引量:2

No association between the polymorphisms of MyD88 gene and sepsis in a Han Chinese population
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摘要 目的探讨髓样分化因子88(myeloid differentiation primary response gene 88,MyD88)多态性位点与脓毒症发生风险及疾病严重程度的关联性。方法采用病例-对照研究设计,Hapmap标签SNPs(haplotype tagging SNP,htSNP)策略,募集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分型技术平台对MyD88基因的标签SNPs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,脓毒症性休克、死亡和器官功能障碍等表型的遗传相关性,以及和脓毒症患者易患风险及环境因素的交互作用。结果 MyD88基因在中国人群中共捕获3个htSNP,其中只有rs7744适用于遗传关联研究。rs7744多态性位点在病例和对照组中的基因型分布均呈Har-dy-Weinberg平衡状态。该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。但在吸烟亚群中携带G/A基因型是携带A/A基因型易患脓毒症风险的2.19倍(95%CI1.13~4.25,P=0.034)。结论在我们的病例对照研究中,MyD88基因多态性位点在脓毒症的发生、发展和病程转归中不发挥重要作用。吸烟是易患脓毒症的独立风险因素。 Objective MyD88(myeloid differentiation factor 88) is the central adapter protein for signal transduction of TLRs(Toll-like receptor) and the interleukin (IL)-1 receptor family that is critical for an effective immune response against a wide range of microbial pathogens and plays a central role in sepsis.In the present study,we investigated whether the polymorphisms of MyD88 gene are associated with the susceptibility to and disease severity of sepsis.Methods We used a case-control genetic association study design to determine if common genetic variation in MyD88 was associated with sepsis risk in a Han Chinese population.Haplotype tagging single nucleotide polymorphisms (htSNPs) were selected from the HapMap database.The htSNPs were genotyped in 255 patients with sepsis and 260 control subjects by the Beckman SNPstream genotyping platform.The associations with the susceptibility to and disease severity of sepsis were estimated by logistic regression,while controlling for confounding factors,including age,sex,smoking status,drinking status,chronic diseases status,APACHE Ⅱ and critical illness status.Results Five MyD88 SNPs were tagged by 3 htSNPs and only rs7744 is fit for genotyping analysis.Genotype frequencies of rs7744 are 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 the polymorphisms and susceptibility to sepsis.Also no significant association with the septic shock,death due to sepsis and the number of organ dysfunction was found with the MyD88 polymorphisms.In smoking subgroup the OR for G/A genotype developing sepsis was 2.19(95% CI 1.13 ~ 4.25,P=0.034) compared with A/A genotype.Conclusions Our findings suggest that the MyD88 gene polymorphisms might not play a major role in mediating susceptibility and disease severity to sepsis,smoking was a independent risk for developing sepsis.
出处 《中华临床医师杂志(电子版)》 CAS 2010年第9期81-87,共7页 Chinese Journal of Clinicians(Electronic Edition)
基金 国家重点基础研究发展规划项目(973计划)(2005CB522602) 北京市科技新星计划项目(2006A54)
关键词 脓毒症 髓样分化因子88 多态性 单核苷酸 连锁不平衡 遗传学 Sepsis; Myeloid differentiation factor 88; Polymorphism,single nucleotide; Linkage disequilibrium; Genetics;
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  • 1Russell JA.Management of sepsis.N Engl J Med,2006,355(16):1699-1713.
  • 2Cohen J.The immunopathogenesis of sepsis.Nature,2002,420(6917):885-891.
  • 3Clark MF,Baudouin SV.A systematic review of the quality of genetic association studies in human sepsis.Intensive Care Mad,2006,32(11):1706-1712.
  • 4Schuetz P,Christ-Craln M,Müiler B.Biomarkers to improve diagnostic and prognostic accuracy in systemic infections.Curr Opin Crit Care,2007,13(5):578-585.
  • 5Adachi O,Kawai T,Takeda K,et al.Targeted disruption of the MyD88 gene results in loss of IL-1 and IL-18-mediated function.Immunity,1998,9(1):143-150.
  • 6Bowie A,O'Neill LA.The interleukin-1 receptor/Toll-like receptor superfamily:signal generators for pro-inflammatory interleukins and microbial products.J X.Leukoc Bid,2000,67(4):508-514.
  • 7Janssons S,Beyaert R.A universal role for MyD88 in TLR/IL-1R-mediated signaling.Trends Biochem Sci,2002,27(9):474-482.
  • 8Leaveer SK,Finney SJ,Burke-Gaffney A,et al.Sepsis since the discovery of Toll-like receptors:disease concepts and therapeutic opportunities.Crit Care Med,2007,35(5):1404-1410.
  • 9Takeda K,Akira S.Toll-like receptors in innate immunity.Int hmmunol,2005,17(1):1-14.
  • 10Dunne A,O'Neill LA.Adaptor usage and Toll-like roceptor signaling specificity.FEBS Lett,2005,579(15):3330-3335.

同被引文献48

  • 1葛金梅,张忠英,彭宣宪,任建林.SNP的研究现状及在MMPs研究中的应用[J].世界华人消化杂志,2005,13(17):2128-2137. 被引量:5
  • 2冷伟建,宋勇,于宝军,施毅.分化抗原簇14基因多态性与感染易感性的相关研究[J].中国危重病急救医学,2007,19(1):17-20. 被引量:2
  • 3张福清,陈国忠.脓毒症的新认识[J].临床军医杂志,2007,35(3):450-452. 被引量:5
  • 4Barie PS, Hydo L J, Pieracci FM, et al. Multiple organ dysfunction syndrome in critical surgical illness. Surg Infect.
  • 5Reid CL, Perrey C, Pravica V, et al. Genetic variation in proinflammatory and anti-inflammatory cytokine produc tion in multiple organ dysfunction syndrome. Crit Care Med, 2002, 30: 2216-2221.
  • 6Liangos O, Jaber BL. Multiple organ dysfunction syndrome in children with sepsis: role of genetic factors. Semin Nephrol,2008,28:499 509.
  • 7O'dwyer M, White M, McManus R, et al. TNF-a promoter single nucleotide polymorphisms may influence gene expression in patients with severe sepsis. Crit Care, 2007,11:p448.
  • 8Ma}etsehak M, Floh6 S, Obertaeke U, et al. Relation of a TNF gene polymorphism to severe sepsis in trauma patients. Ann Surg, 1999,230: 207-214.
  • 9Wen AQ,Gu W,Wang J,et al. Clinical relevance of IL-lbeta promoter poly morphisms ( 1470,--511,and --31) in patients with major trauma. Shock, 2010,33:576-582.
  • 10Arnalich F, L6pez - Maderuelo D, Codoceo R,et al. Interleukin-1 receptor antagonist gene polymorphism and mortality in patients with severe sepsis. Clin Exp Immunol, 2002, 127 : 331-336.

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