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.摘要: 背景 这项meta分析的目的是调查常见的1型糖尿病以及2型糖尿病基因变异(蛋白酪氨酸磷酸酯酶22[PTPN22] rs2476601C/T、胰岛素[INS] rs689A/T以及转录因子7样-2[TCF7L2] rs7903146C/T)与成人迟发型自身免疫性糖尿病(latent autoimmune diabetes in adults,LADA)之间的关系。 方法 对截至2017年的电子数据库进行了系统搜索,并且汇总了涉及到这3种基因变异的16项独立病例对照研究的数据。为了评估相关性强度,使用汇总的每种1型糖尿病以及2型糖尿病基因变异的等位基因以及基因型频率来计算优势比(ORs)与95%置信区间(CIs)。对所有的研究都进行异质性检验并评估发表偏倚。 结果 在这项分析中共汇总了来自16个病例对照研究的8869名病例与20829名对照者。对于rs2476601来说,纯合子TT(OR为2.67;95% CI为1.92-3.70;P0.0001)、杂合子CT(OR为1.61;95% CI为1.44-1.79;P0.0001)以及T等位基因(OR为1.62;95% CI为1.48-1.78;P0.0001)都与LADA有显著的相关性。总体而言,对于rs689来说,TT基因型(OR为0.43;95% CI为0.30-0.64;P0.0001)、AT基因型(OR为0.53;95% CI为0.45-0.62;P0.0001)以及T等位基因(OR为0.61;95% CI为0.52-0.71;P0.0001 )与LADA都呈显著负相关。对于rs7903146多态性来说,T等位基因(OR为1.19;95% CI为1.00-1.40;P = 0.04)可能与LADA风险相关。 结论 本研究发现rs2476601C/T、rs689A/T以及rs7903146C/T的多态性与LADA的风险相关。由此表明,从遗传学上来说,LADA可能是T1D与T2D的混合体。.