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

Abstract

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.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 IL1Ra SNPs on overall disease susceptibility.

The association between ADAM12 gene polymorphisms and osteoarthritis: an updated meta-analysis

“…In recent years, many researchers have attempted to explore the causes of OA at the genetic level, and a variety of genes that may be associated with OA have been identified, including ADAM12, vitamin D receptor, matrix metalloproteinases, estrogen receptor, and interleukins [5][6][7][8]. Currently, it has been found that the mutation of IL-1Ra Ser133Ser does not appear to be associated with immune-mediated and inflammatory diseases in a variety of genetic patterns, suggesting that the mutant allele C of IL-1Ra Ser133Ser does not increase the risk of disease [9]. Studies have also shown that mutations in inflammatory cytokines (G allele at rs361525, T allele at rs419598, and A allele at rs2228145) can lead to increased prevalence of coronavirus disease 2019 [10].…”

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