Association of genetic variants in the IRAK-4 gene with susceptibility to severe sepsis

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.