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

Area of Science:

• Immunogenetics
• Molecular Epidemiology

Background:

• Conflicting evidence exists on the association between interleukin-1 (IL-1) polymorphisms and sepsis susceptibility.
• Previous epidemiological studies have yielded inconsistent results.

Purpose of the Study:

• To conduct a meta-analysis evaluating the association between various interleukin-1 (IL-1) gene polymorphisms and the risk of developing sepsis.
• To synthesize existing data to clarify the role of IL-1 genetic variations in sepsis susceptibility.

Main Methods:

• A systematic literature search was performed across PubMed, Embase, and Web of Knowledge databases up to June 15, 2013.
• A random-effects model was used to calculate pooled odds ratios (OR) and 95% confidence intervals (CI) for assessing associations.
• Subgroup analyses were conducted based on ethnicity, sepsis severity, and study quality scores.

Main Results:

• Eighteen studies involving five IL-1 polymorphisms were analyzed.
• Significant associations with sepsis susceptibility were found for IL-1A-889 (allelic effect, OR = 1.47) and IL-1RN VNTR (allelic effect, OR = 1.40).
• The IL-1B + 3954 polymorphism (genotype TT) showed a decreased risk of sepsis (OR = 0.59), particularly in Caucasian populations and in sepsis subgroups.

Conclusions:

• Interleukin-1 gene polymorphisms IL-1A-889, IL-1B + 3954, and IL-1RN VNTR may be associated with sepsis susceptibility.
• The effect of IL-1RN VNTR on sepsis risk appears to increase with disease severity.
• Larger, homogenous population studies are recommended for validation of these findings.