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

J Diabetes. 2019 Jun;11(6):484-496. doi: 10.1111/1753-0407.12879. Epub 2018 Dec 12.

Abstract

Background: 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).

Methods: 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.

Results: 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.

Conclusion: 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;P < 0.0001)、杂合子CT(OR为1.61;95% CI为1.44-1.79;P < 0.0001)以及T等位基因(OR为1.62;95% CI为1.48-1.78;P < 0.0001)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;P < 0.0001)、AT基因型(OR为0.53;95% CI为0.45-0.62;P < 0.0001)以及T等位基因(OR为0.61;95% CI为0.52-0.71;P < 0.0001 )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。.

Keywords: INS; LADA; PTPN22; TCF7L2; meta-analysis; meta分析; polymorphism; 多态性.

Publication types

  • Meta-Analysis

MeSH terms

  • Adult
  • Biomarkers / analysis
  • Case-Control Studies
  • Diabetes Mellitus, Type 1 / genetics*
  • Diabetes Mellitus, Type 1 / pathology
  • Diabetes Mellitus, Type 2 / genetics*
  • Diabetes Mellitus, Type 2 / pathology
  • Follow-Up Studies
  • Genetic Predisposition to Disease
  • Genotype
  • Humans
  • Insulin / genetics*
  • Latent Autoimmune Diabetes in Adults / genetics*
  • Latent Autoimmune Diabetes in Adults / pathology
  • Polymorphism, Single Nucleotide*
  • Prognosis
  • Protein Tyrosine Phosphatase, Non-Receptor Type 22 / genetics*
  • Transcription Factor 7-Like 2 Protein / genetics*

Substances

  • Biomarkers
  • Insulin
  • TCF7L2 protein, human
  • Transcription Factor 7-Like 2 Protein
  • PTPN22 protein, human
  • Protein Tyrosine Phosphatase, Non-Receptor Type 22