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Published data on the association between interleukin (IL)-18 gene polymorphisms (-137 C/G, -607 A/C) and type 1 diabetes (T1D) risk are inconclusive. To obtain a more precise estimation of the association between the IL-18 gene polymorphisms and T1D, a meta-analysis was performed. A total of 11 studies including 5,945 cases and 6,404 controls were included in the analysis of the association between -137 C/G and T1D risk. No significant association between -137 C/G and T1D risk was observed in the total population [C vs. G: odds ratio (OR)=1.02, 95% confidence interval (CI)=0.87-1.20; CC + CG vs. GG: OR=1.05, 95% CI=0.87-1.25; CC vs. CG + GG: OR=0.96, 95% CI=0.68-1.36]. No significant association was identified in the stratified analysis for all the genetic models in the European population. Concerning -607 A/C, 10 studies involving 3,048 patients and 3,377 controls were included in this meta-analysis. When all the studies were pooled, the results showed no evidence for a significant association between IL-18 -607 A/C polymorphism and T1D risk (A vs. C: OR=0.93, 95% CI=0.81-1.06; AA + AC vs. CC: OR=0.99, 95% CI=0.89-1.10; AA vs. AC + CC: OR=0.81, 95% CI=0.60-1.09). In addition, similar results were obtained in the subgroup analysis based on ethnicity. In summary, the present meta-analysis suggests a lack of association between the two polymorphisms (-137 C/G, -607 A/C) in the IL-18 gene and T1D. Due to the limitation of the number of the studies, the conclusions drawn should be considered with caution. Larger scale primary studies are required to evaluate the association between IL-18 gene polymorphisms and T1D.

Association of the interleukin-18 −137 C/G, −607 A/C polymorphisms with type 1 diabetes: A meta-analysis