Associations between TNF gene polymorphisms (-308 A/G, -238 A/G, -1031 C/T and -857 T/C) and genetic susceptibility to T1D: a meta-analysis.

The aim of this study was to estimate the associations between tumor necrosis factor (TNF) gene polymorphisms and type 1 diabetes (T1D) using meta-analysis. Relevant studies were searched using PubMed and Embase up to August 2013. A total of 32 comparisons from 21 studies examining the associations between TNF polymorphisms and T1D were included in the present meta-analysis. Our meta-analysis identified a significant association between TNF -308 A/G polymorphism A allele and T1D in all subjects [odds ratio (OR) 2.001, 95 % confidence interval (CI) 1.732-2.312). Significant associations of AA and AA+AG genotype of TNF -308 A/G polymorphism with genetic susceptibility to T1D were also found (OR 3.203, 95 % CI 2.373-4.324; OR 2.232, 95 % CI 1.881-2.649). After stratification by ethnicity, significant associations of T1D with TNF -308 A/G polymorphism under all genetic models (A allele and AA, AA+AG genotype) were still detected in European (OR 1.952, 95 % CI 1.675-2.274; OR 3.108, 95 % CI 2.169-4.455; OR 2.249, 95 % CI 1.870-2.706, respectively) and non-European populations (OR 2.152, 95 % CI 1.488-3.112; OR 3.439, 95 % CI 2.000-5.914; OR 2.207, 95 % CI 1.496-3.257, respectively). Our meta-analysis also revealed an association of TNF -857 T/C polymorphism T allele with T1D risk (OR 1.647, 95 % CI 1.431-1.896). Furthermore, analysis of TT and TT+TC genotype indicated the same result patterns as shown by the TNF -857 T/C polymorphism T allele (OR 2.206, 95 % CI 1.467-3.317; OR 1.762, 95 % CI 1.490-2.083). In conclusion, our meta-analysis results indicate that TNF -308 A/G and -857 T/C polymorphisms are involved in the genetic background of T1D.