Interleukin-18 promoter -607 C/A and -137 G/C polymorphisms and susceptibility to type 1 diabetes: A meta-analysis

Objective: The aim of this study was to determine whether the functional interleukin-18 (IL-18) promoter -607 C/A (rs1946518) and -137 G/C (rs187238) polymorphisms are associated with susceptibility to type 1 diabetes (TID). Methods: A meta-analysis was conducted to assess the associations between the IL-18-607 C/A and -137 G/C polymorphisms and T1D in overall and by ethnic group. Results: A total of 6075 cases and 5744 controls from ten studies were considered in this meta-analysis. In all study subjects, the meta-analysis showed no association between T1D and the IL-18-607 C allele (OR = 1.083, 95% CI = 0.930-1.260, p = 0.307). However, stratification by ethnicity indicated an association between the IL-18-607 C allele and T1D in Asians (OR = 1.506, 95% CI = 1.172-1.936, p = 0.001), but not in Europeans (OR = 0.988, 95% CI = 0.808-1.209, p = 0.907). Analysis using recessive and dominant models and homozygote contrast showed the same -607 C allele pattern in Asians and Europeans. Meta-analysis of the IL-18-137 G/C polymorphism showed no association between T1D and the IL-18-137 G allele in all study subjects (OR = 1.066, 95% CI = 0.926-1.2289, p = 0.375). Stratification by ethnicity indicated no association between the IL-18-137 G allele and T1D in Europeans and Asians (OR = 1.021, 95% CI = 0.961-1.085, p = 0.504; OR = 0.851, 95% CI = 0.5821-1.245, p = 0.406). Conclusions: Our meta-analysis demonstrates that the IL-18-607 C/A polymorphism may be associated with susceptibility to T1D in Asians, but not in Europeans.