Association of IL-1Ra Ser133Ser Variant with Susceptibility to Immune-Mediated and Inflammatory Diseases: A Meta-Analysis of 2622 Cases and 3854 Controls

BACKGROUND: The rs315952 (Ser133Ser) has been reported to influence the risk for immune-mediated as well as inflammatory diseases in many studies; however, the results remain inconsistent. The current meta-analysis was performed to give a more precise estimation for the relationship between this IL-1Ra missense variant and the risk of both types of diseases. METHODS: Relevant publications were retrieved through a literature search in Web of Science, Medline, PubMed, Scopus, EMBASE, and Google scholar search engines, between 2000 and 2019. Odds ratios (ORs) with 95% confidence intervals (CIs) were calculated to assess the strength of the association. RESULTS: Twenty-two studies, including 2622 cases with and 3854 controls were identified. The IL-1Ra Ser133Ser variant does not confer an increased overall risk for immune-mediated and inflammatory diseases. This variant was statistically associated with decreased risk of systemic lupus erythematosus (under allelic, codominant heterozygous, and dominant models) or ankylosing spondylitis (in allelic and recessive models)(OR<1). Moreover, alleles, as well as genotypes of the IL-1Ra Ser133Ser variant, may confer an increased risk of immune-mediated and inflammatory diseases in Hispanics. However, this variant was not associated with susceptibility to immune-mediated and inflammatory diseases in both Asians and Arabs. CONCLUSION: The pooled results fail to support the hypothesis that the IL-1Ra Ser133Ser variant is associated with the overall risk of immune-mediated and inflammatory diseases. Performing large scale replication and meta-analysis of functional variants within this gene is encouraged to further investigate the influence of IL-1Ra SNPs on overall disease susceptibility.