Association Between CD14Promoter Polymorphism And Susceptibility To Sepsis And Sepsis Mortality:a Meta-analysis

OBJECTIVE:Genetic polymorphism of innate immune system is believed to be associated with sepsis. CD14is a major part of the innate immune system, and Several single nucleotide polymorphisms has been identified inside the CD14promoter sequence. The CD14-159(-260)C/T polymorphism has been reported to be associated with sepsis with inconsistent results. We conducted a systematic review and meta-analysis to determine whether the polymorphism confers susceptibility to sepsis or is associated with increased risk of death from sepsis.METHODS:A systematic search was performed in Pubmed, EMBASE, Web of Science and CNKI databases. Two reviewers independently selected studies on the genetic association of CD14-159C/T polymorphism with sepsis and data was extracted onto standardized forms. Methodological quality was assessed by both reviewers. Fixed or random effect method was adopted based on heterogeneity. Stratified analyses were conducted by different variables. To further investigate the heterogeneity, Meta-regression and sensitivity analysis were performed. Publication bias was examined using Begg’s and Egger’s test.RESULTS:Twenty-one studies were included based on predefined inclusion criteria. All were of reasonable methodological quality. As compared to CC, the CD14-159TT+TC genotypes were significantly associated with an increased development of sepsis in the overall population (OR=1.39,95%CI1.15-1.68, p<0.05). Stratification by ethnicity indicated that the contribution to sepsis susceptibility may be stronger in Asian (TT+TC Vs. CC OR1.57,95%CI1.22-2.08, p<0.05) than in other ethnicities. When stratified for underlying condition, an significant risk for sepsis were among burnt patient.(OR=1.95,95%CI1.12-3.42, p<0.05). There was no association between the polymorphism genotype and mortality from sepsis (TT+TC Vs. CC OR1.26,95%CI0.82-1.94, p=0.30). Ethnics contributes most heterogeneity according to Meta-regression. No significant publication bias was found.CONCLUSIONS:Our systematic review and meta-analysis demonstrates that the CD14-159C/T polymorphism polymorphism is associated with sepsis susceptibility. However, it is not associated with sepsis mortality.