Associations between interleukin-1 gene polymorphisms and sepsis risk: a meta-analysis

Abstract

BackgroundPrevious epidemiological studies have presented conflicting evidence regarding associations between interleukin-1 (IL-1) polymorphisms and sepsis susceptibility. We have performed a meta-analysis to evaluate possible associations between IL-1 polymorphisms and sepsis risk.MethodsEligible literature was retrieved from PubMed, Embase and Web of Knowledge databases until Jun 15, 2013. The pooled odds ratio (OR) and 95% confidence interval (CI) were calculated using random-effects model in the overall and subgroup analysis based on ethnicity, sepsis severity and quality score.ResultsEighteen studies addressing five IL-1 polymorphisms were included in this meta-analysis. For IL-1A-889 (rs1800587) polymorphism, significant association was observed in overall comparison for allelic effect (OR = 1.47, 95% CI = 1.01-2.13, P = 0.04). There were no significant associations between either IL-1B-511 (rs16944) or IL-1B-31 (rs1143627) and sepsis susceptibility in overall or subgroup analyses. For IL-1B + 3594 (rs143634) polymorphism, genotype TT decreased sepsis risk in overall analysis (OR = 0.59, 95% CI = 0.36-0.97, P = 0.04), as well as in Caucasian (OR = 0.57, 95% CI = 0.34-0.95, P = 0.03) and sepsis (OR = 0.55, 95% CI = 0.31-0.97, P = 0.04) subgroup analysis. For IL-1RN VNTR polymorphism, significant association was observed in overall comparison for allelic effect (OR = 1.40, 95% CI = 1.01-1.95, P = 0.04). Furthermore, the effect sizes of IL-1RN VNTR on sepsis risk increased with disease severity (septic shock OR > severe sepsis OR > sepsis OR).ConclusionsOur meta-analysis indicated that IL-1A-889, IL-1B + 3954 and IL-1RN VNTR might be associated with sepsis susceptibility. However, further studies with larger sample sizes and from homogenous populations would be necessary to validate these findings.

IL‐1B rs16944 polymorphism is related to septic shock and death

“…This process is critical in the pathogenesis of sepsis and septic shock. Moreover, sepsis susceptibility or resistance has been related to genetic variations within this gene . In our study, the presence of the minor rs16944 A allele in homozygosis was related to the onset of septic shock and death (septic shock‐related death).…”

“…Conversely, AA genotype has showed a reduced Aspergillusinduced IL-1b production and TNF a secretion by PBMCs [21]. However, there are some discrepancies as some studies did not find any genetic association of rs16944 with IL-1b levels [20], infection or sepsis [3,23,27,37]. In non-European population, the rs16944 AA genotype has been related to lower risk of infection [19], and the GG genotype was associated with production of IL-1b [38] and higher risk of infection [24,38].…”

“… found that IL‐1B rs16944 polymorphism is not associated with the clinical course of sepsis. Besides, a recent meta‐analysis did not find significant association between IL‐1B rs16944 polymorphism and sepsis risk . Thus, there are certain discrepancies about the relationship between IL‐1B rs16944 and sepsis in the literature, and further studies would be needed.…”

Clinical associations of host genetic variations in the genes of cytokines in critically ill patients

“…Invitro studies have shown that allele A in the promoter (upstream of the transcriptional start site) SNP 2511 G>A is related to increased lipopolysaccharide (LPS)induced IL-1B protein secretion [36]. In a recent metaanalysis, the SNP 2511A allele was less frequent in patients with sepsis compared to controls among Caucasians (one study) and Asians (four studies), although the results failed to reach statistical significance [37]. The same direction of the effect was observed in our study for the same genetic model.…”

Interleukin 1α and 1β gene variations are associated with tuberculosis in silica exposed subjects

“…Besides silicosis, this polymorphism has been previously associated with the modulation of the severity of other inflammatory diseases, such as Hashimoto's thyroiditis, Graves’ disease, periodontitis, and rheumatoid arthritis . Second, the −889C/T (rs1800587) SNP is located in the 5′‐untranslated region (5′‐UTR) of the IL1A gene and plays an important role in the transcriptional regulation of the gene, leading to an increased serum protein level . This polymorphism was previously associated with periodontitis, sepsis, and allergic rhinitis .…”