Interleukin-18 Gene Polymorphisms and Rheumatoid Arthritis Susceptibility: An Umbrella Review of Meta-Analyses

This study systematically analyzes the association between interleukin-18 (IL-18) gene polymorphisms and rheumatoid arthritis (RA) susceptibility. The electronic databases Ovid MEDLINE, Ovid Excerpta Medica Database, and Cochrane Library were searched to identify meta-analyses that included case-control studies reporting IL-18 gene polymorphisms and RA susceptibility. Data were reanalyzed using Review Manager Software 5.1, and Mantel-Haenszel random effects were applied for the five genetic models: allelic, recessive, dominant, homozygote, and heterozygote. The effect size of odds ratios (ORs) and their corresponding 95% confidence interval (CI) were calculated. A total of seven meta-analyses with poor quality were included. The IL-18 polymorphisms -607 A/C, -137 C/G, -920 T/C, and -105 C/A have been reported. With weak evidence, IL-18 -607 A/C polymorphisms were associated with a reduced risk of RA susceptibility using the allele model (OR = 0.76, 95% CI: 0.61 - 0.93, p=0.01), dominant model (OR = 0.67, 95% CI: 0.50 - 0.90, p=0.008), homozygote model (OR = 0.57, 95% CI: 0.35 - 0.91, p=0.02), and heterozygote model (OR = 0.71, 95% CI: 0.54 - 0.93, p=0.01) in the overall population. IL-18 gene polymorphisms and RA susceptibility are affected by ethnicity: With weak evidence, IL-18 -137 C/G polymorphisms were related to reduce RA susceptibility in the Asian population (allele model: OR = 0.59, 95% CI: 0.40 - 0.88, p=0.01; dominant model: OR = 0.57, 95% CI: 0.37 - 0.89, p=0.01; heterozygote model: OR = 0.60, 95% CI: 0.38 - 0.94, p=0.03). IL-18 -607 A/C gene polymorphisms are a protective factor for RA susceptibility in the overall population, and IL-18 -137 C/G gene polymorphisms are a protective factor for RA susceptibility in the Asian population. Further studies are needed to confirm these results owing to the limitations of the included studies.