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Abstract
BackgroundRecent studies on the association between CD14-159C/T polymorphism and sepsis showed inconclusive results. Accordingly, we conducted a comprehensive literature search and a meta-analysis to determine whether the CD14-159C/T polymorphism conferred susceptibility to sepsis or was associated with increased risk of death from sepsis.MethodologyData were collected from the following electronic databases: PubMed, Embase, Medline, Web of Knowledge, and HuGE Navigator, with the last report up to June 15, 2012. The odds ratio (OR) and 95% confidence interval (CI) were used to assess the strength of association. We summarized the data on the association between CD14-159C/T polymorphism and sepsis in the overall population and subgroup by ethnicity and sepsis subtype.Principal FindingsA total of 16 studies on sepsis morbidity (1369 cases and 2382 controls) and 4 studies on sepsis mortality (731 sepsis patients) met the inclusion criteria for meta-analysis. Overall analysis showed no strong evidences of association with sepsis susceptibility under any genetic model. However, slight associations were found in Asian populations (dominant model: OR = 1.38, 95%CI = 0.96–1.98, P = 0.08) and septic shock patients (dominant model: OR = 1.72, 95%CI 1.05–2.83, P = 0.03; allelic model: OR = 1.52, 95%CI 1.09–2.12, P = 0.01) in the stratified analysis. Moreover, there was borderline association between CD14-159C/T and sepsis mortality under the dominant genetic model (OR = 1.44, 95%CI = 0.98–2.11, P = 0.06).Conclusions/SignificanceThis meta-analysis suggests that the CD14-159C/T polymorphism may not be a significant susceptibility factor in the risk of sepsis and mortality. Only weak associations were observed in Asian populations and septic shock patients. More studies based on larger sample sizes and homogeneous sepsis patients are needed to confirm these findings.
Highlights
Sepsis is regarded as a condition of systemic inappropriate inflammation response of the host organism to the invasion of microorganisms, which is the leading cause of death in critically ill patients
HuGE Navigator databases were searched in order to identify all published case-control studies up to June 15 2012 that had evaluated the associations between Cluster of differentiation 14 (CD14) polymorphism and sepsis
The Medical Subject Headings and key words used for search were ‘‘CD14 or cluster of differentiation-14’’ and ‘‘sepsis or severe sepsis or septic shock or septicemia’’ and ‘‘polymorphism or variant or mutation’’
Summary
Sepsis is regarded as a condition of systemic inappropriate inflammation response of the host organism to the invasion of microorganisms, which is the leading cause of death in critically ill patients. Pathogen invasion is important determinant of sepsis, it is difficult to identify prognostic factors that may predict susceptibility and mortality in sepsis. A study of adoptees, for example, indicated a substantial inherited increase in the risk of premature death from infection [1]. Large number of publications aim at association of genetic polymorphism and sepsis [2]. These polymorphisms mainly include variants in genes coding for proteins involved in the recognition of bacterial pathogens and response to bacterial pathogens. Recent studies on the association between CD14-159C/T polymorphism and sepsis showed inconclusive results. We conducted a comprehensive literature search and a meta-analysis to determine whether the CD14159C/T polymorphism conferred susceptibility to sepsis or was associated with increased risk of death from sepsis
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