The Association Polymorphisms Of Toll-Like Receptor4and Cluster Of Differentiation14Genes And Susceptibility To Sepsis

Backgrounds and objective:Sepsis is defined as the presence of SIRS (systemic inflammation response syndrome, SIRS) caused by infection. The incidence and mortality of sepsis is high. Currently, Sepsis has become the leading cause of death in non-cardiovascular intensive care unit (ICU). Although the pathogenesis of sepsis is not very clear, there are evidences that the incidence of sepsis is not only associated with environmental factors, but also with genetic factors. During the process of the interaction between the organism and the pathogenic microorganisms, the mutation of genes which participate in the immune response, especially the single nucleotide polymorphism (SNPs), may influence the host immune response to pathogenic microorganisms. Toll-like receptor4(TLR4) and cluster of differentiation14(CD14) are important pathogen recognition receptors (PRRs) in the immune response, and they play an important role in the process of sepsis. This study was to investigate the correlation of multiple SNPs in TLR4and CD14with sepsis, to investigate which SNP may be associated with the incidence of sepsis, and to analyze its role in the occurrence of sepsis. Method:In order to evaluate whether the eight SNPs in TLR4and CD14gene were associated with the susceptibility to sepsis, the polymerase chain reaction-single base extension (PCR-SBE) and DNA sequencing were used to analyze the SNPs of TLR4(rs10759932, rs11536889, rs7873784, rs12377632, rs1927907, rs1153879) and CD14(rs2569190and rs2563298) in sepsis in Guangxi. Results:In this study, one hundred and fifty two patients with sepsis and one hundred and ninty nine control people were enrolled. There were no significant differences in gender and age between the case and control group. Compare to the control group, rs11536889polymorphism in TLR4and rs2563298polymorphism in CD14were significantly associated with the risk of sepsis. The frequencies of rs11536889polymorphism and rs2563298polymorphism in the case group were higher than that in the control group (OR=1.430,95%CI,1.032-1.981, P<0.05, OR=2.454,95%CI,1.458-4.130, P<0.05, respectively). However, compared with the control group, the frequencies of the other six SNPs in TLR4and CD14gene did not change significantly in the case group.Conclusion:Rs11536889polymorphism in TLR4and rs2563298polymorphism in CD14may be associated with the susceptibility to sepsis.