Association between IL-6-174G/C Polymorphism and the Risk of Sepsis and Mortality: A Systematic Review and Meta-Analysis

Abstract

BackgroundRecent studies have reported the association between IL-6-174G/C polymorphism and sepsis. However, the results are inconclusive and conflicting. To better understand the role of IL-6-174G/C polymorphism in sepsis, we conducted a comprehensive meta-analysis.MethodologyLiterature search was conducted through PubMed, Embase, Web of Knowledge databases until July 29, 2013. The pooled odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using fixed- or random-effect model based on heterogeneity test in total and subgroup analyses.ResultsTwenty studies on the risk of sepsis and seven studies on sepsis mortality were included. None of the results showed evidence of a significant association between IL-6-174G/C polymorphism and sepsis risk in overall analysis or subgroup analyses based on sepsis type, ethnicity, source of control and age under any genetic model (the allele comparison, the codominant, the recessive or the dominant model). Although there was a statistically significant association between IL-6-174 G/C polymorphism and sepsis-related mortality under the recessive model, the significance did not exist after Bonferroni’s correction.ConclusionsCurrent evidence does not support a direct effect of IL-6-174 G/C polymorphism on the risk of sepsis. In addition, there was no association between IL-6-174 G/C polymorphism and sepsis mortality after Bonferroni’s correction. Further analyses of gene-environment interactions and more studies based on larger sample size and homogeneous sepsis patients are required.

Association between -174G/C and -572G/C interleukin 6 gene polymorphisms and severe radiographic damage to the hands of Mexican patients with rheumatoid arthritis: a preliminary report

“…Our results are in accordance with the findings described by Gao et al (2015), who conducted a meta-analysis comparing the frequency of the IL6 gene -174G/C polymorphism in different populations with sepsis and healthy controls, where was reported that GG was the most frequent genotype in the control group.…”

IL-6 gene polymorphisms and sepsis in icu adult romanian patients: a prospective study

“…In adults, most authors invalidated this association in different populations: in severe septic adults, including surgical sepsis (31,32), in patients with chronic nephropathy (17), and in systemic infections of uncertain meningococcal and pneumococcal etiology (13,33). A recent meta-analysis conducted by Gao et al strongly demonstrated the lack of evidence of a significant association between IL-6 -174 G/C and sepsis risk, this being consistent with our results (8).…”

“…Lack of IL-6 -174 G/C polymorphism association with sepsis mortality is supported by the meta-analysis conducted by Gao et al on seven studies, with only one positive correlation with the recessive model (CC vs GC/GG), prior to Bonferroni correction (8).…”

“…It has been demonstrated that certain single nucleotide polymorphisms (SNPs) in cytokines genes are associated with the risk of sepsis occurrence and its outcome (8). Recent studies have reinforced the idea of a possible genetic basis for the selection of patients with favorable potential response to personalized therapies, with a growing interest in identification of a sepsis-associated genetic predisposition (9).…”

The role of genetics and antibodies in sepsis

“…A metaanalysis of 12 case-control studies failed to demonstrate a real effect of carriage of minor frequency C alleles on sepsis risk (18). However, considerable heterogeneity exists in these studies as patients of European and African ancestry were analyzed together and the control groups were also very heterogeneous.…”