BACKGROUND:The association of genetic variation in the IRAK-1 gene with sepsis outcome has been proved.However,few studies have addressed the impact of the IRAK-4 gene variants on sepsis risk.This study aimed to deter...BACKGROUND:The association of genetic variation in the IRAK-1 gene with sepsis outcome has been proved.However,few studies have addressed the impact of the IRAK-4 gene variants on sepsis risk.This study aimed to determine whether the polymorphisms in the IRAK-4 gene are associated with susceptibility to and prognosis of severe sepsis in the Chinese Han ethnic population.METHODS:In this case-control study,192 patients with severe sepsis hospitalized in the emergency department of Zhongshan Hospital from February 2006 to December 2009 and 192healthy volunteers were enrolled.Exclusion criteria included metastatic tumors,autoimmune diseases,AIDS or treatment with immunosuppressive drugs.This study was approved by the ethical committee of Zhongshan Hospital,Fudan University.Sepsis patients were divided into a survival group(n=124)and a non-survival group(n=68)according to the 30-day mortality.Primer 3 software was used to design PCR and sequencing primers.Genomic DNA was extracted from peripheral blood mononuclear cells.Seven tagSNPs in IRAK-4 were selected according to the data of the Chinese Han population in Beijing from the Hapmap project and genotyped by direct sequencing.The chi-square test was used to evaluate the differences in genotype and allele frequencies between the two groups.RESULTS:The distributions of all tagSNPs were consistent with Hardy-Weinberg equilibrium.The allele and genotype frequencies of rs4251545(G/A)were significantly different between the severe sepsis and healthy control groups(P=0.015,P=0.035,respectively).Carriers of the rs4251545A had a higher risk for severe sepsis compared with carriers of the rs4251545G(OR=1.69,95%CI:1.10-2.58).The allele and genotype frequencies of all SNPs were not significantly different between the survival group and non-survival group.CONCLUSION:These findings indicate that the variants in IRAK-4 are significantly associated with susceptibility to severe sepsis in the Chinese Han ethnic population.展开更多
目的：通过研究尿酸性肾病动物模型中白介素-1（IL-1）β和白介素-1受体相关激酶4（IRAK-4）表达的意义,了解IL-1β信号通路在尿酸性肾病中的作用。方法：Wistar大鼠54只随机分为高尿酸血症组30只、正常组24只,制备尿酸性肾病大鼠模型,...目的：通过研究尿酸性肾病动物模型中白介素-1（IL-1）β和白介素-1受体相关激酶4（IRAK-4）表达的意义,了解IL-1β信号通路在尿酸性肾病中的作用。方法：Wistar大鼠54只随机分为高尿酸血症组30只、正常组24只,制备尿酸性肾病大鼠模型,检测尿酸（UA）、尿素氮（BUN）、肌酐（CR）及肌酐清除率（Ccr）、24 h尿微量白蛋白（m A1b）;取肾脏组织行HE染色,观察形态学变化;免疫组化测定IL-1β的表达;荧光定量PCR检测IRAK-4 m RNA的水平。结果：高尿酸组2、4、6周时IL-1β的表达均增加,免疫组化评分（IHS）均明显升高（P〈0.01）;高尿酸血症组较正常组IRAK-4 m RNA在2、4、6周时均出现表达上调,4~6周IRAK-4 m RNA表达明显增加,与正常组比较有显著性差异（P〈0.01）。结论：IL-1β、IRAK-4参与了尿酸性肾病炎症反应的过程,可能为尿酸性肾病治疗提供新的可能。展开更多
文摘BACKGROUND:The association of genetic variation in the IRAK-1 gene with sepsis outcome has been proved.However,few studies have addressed the impact of the IRAK-4 gene variants on sepsis risk.This study aimed to determine whether the polymorphisms in the IRAK-4 gene are associated with susceptibility to and prognosis of severe sepsis in the Chinese Han ethnic population.METHODS:In this case-control study,192 patients with severe sepsis hospitalized in the emergency department of Zhongshan Hospital from February 2006 to December 2009 and 192healthy volunteers were enrolled.Exclusion criteria included metastatic tumors,autoimmune diseases,AIDS or treatment with immunosuppressive drugs.This study was approved by the ethical committee of Zhongshan Hospital,Fudan University.Sepsis patients were divided into a survival group(n=124)and a non-survival group(n=68)according to the 30-day mortality.Primer 3 software was used to design PCR and sequencing primers.Genomic DNA was extracted from peripheral blood mononuclear cells.Seven tagSNPs in IRAK-4 were selected according to the data of the Chinese Han population in Beijing from the Hapmap project and genotyped by direct sequencing.The chi-square test was used to evaluate the differences in genotype and allele frequencies between the two groups.RESULTS:The distributions of all tagSNPs were consistent with Hardy-Weinberg equilibrium.The allele and genotype frequencies of rs4251545(G/A)were significantly different between the severe sepsis and healthy control groups(P=0.015,P=0.035,respectively).Carriers of the rs4251545A had a higher risk for severe sepsis compared with carriers of the rs4251545G(OR=1.69,95%CI:1.10-2.58).The allele and genotype frequencies of all SNPs were not significantly different between the survival group and non-survival group.CONCLUSION:These findings indicate that the variants in IRAK-4 are significantly associated with susceptibility to severe sepsis in the Chinese Han ethnic population.
文摘目的：通过研究尿酸性肾病动物模型中白介素-1（IL-1）β和白介素-1受体相关激酶4（IRAK-4）表达的意义,了解IL-1β信号通路在尿酸性肾病中的作用。方法：Wistar大鼠54只随机分为高尿酸血症组30只、正常组24只,制备尿酸性肾病大鼠模型,检测尿酸（UA）、尿素氮（BUN）、肌酐（CR）及肌酐清除率（Ccr）、24 h尿微量白蛋白（m A1b）;取肾脏组织行HE染色,观察形态学变化;免疫组化测定IL-1β的表达;荧光定量PCR检测IRAK-4 m RNA的水平。结果：高尿酸组2、4、6周时IL-1β的表达均增加,免疫组化评分（IHS）均明显升高（P〈0.01）;高尿酸血症组较正常组IRAK-4 m RNA在2、4、6周时均出现表达上调,4~6周IRAK-4 m RNA表达明显增加,与正常组比较有显著性差异（P〈0.01）。结论：IL-1β、IRAK-4参与了尿酸性肾病炎症反应的过程,可能为尿酸性肾病治疗提供新的可能。
