Association of common type 1 and type 2 diabetes gene variants with latent autoimmune diabetes in adults: A meta-analysis.

Abstract

The aim of this meta-analysis was to determine the association of common type 1 diabetes (T1D) and type 2 diabetes (T2D) gene variants (protein tyrosine phosphatase non-receptor 22 [PTPN22] rs2476601C/T, insulin [INS] rs689A/T and transcription factor 7-like 2 [TCF7L2] rs7903146C/T) with latent autoimmune diabetes in adults (LADA). A systematic search of electronic databases was conducted up to 2017 and data from 16 independent case-control studies for three gene variants were pooled. The pooled allele and genotype frequencies for each T1D and T2D gene variant were used to calculate odds ratios (ORs) with 95% confidence intervals (CIs) to assess the strength of the association. Heterogeneity tests and evaluation of publication bias were performed for all studies. In all, 8869 cases and 20 829 controls pooled from 16 case-control studies were included in the analysis. For rs2476601, a significant association was found for homozygote TT (OR 2.67; 95% CI 1.92-3.70; P < 0.0001), heterozygote CT (OR 1.61; 95% CI 1.44-1.79; P < 0.0001), and the T allele (OR 1.62; 95% CI 1.48-1.78; P < 0.0001). Overall, a significant inverse association was observed for rs689 in the TT genotype (OR 0.43; 95% CI 0.30-0.64; P < 0.0001), AT genotype (OR 0.53; 95% CI 0.45-0.62; P < 0.0001), and T allele (OR 0.61; 95% CI 0.52-0.71; P < 0.0001). For the rs7903146 polymorphism, the T allele (OR 1.19; 95% CI 1.00-1.40; P = 0.04) may be associated with the risk of LADA. The rs2476601C/T, rs689A/T, and rs7903146C/T polymorphisms were found to be associated with the risk of LADA, thereby indicating that, genetically, LADA could be an admixture of both T1D and T2D.