Clinical signs of type 1 diabetes are associated with type 2 diabetes marker transcription factor 7-like 2 polymorphism

J Diabetes Investig. 2023 Feb;14(2):221-229. doi: 10.1111/jdi.13933. Epub 2022 Oct 27.

Abstract

Aims/introduction: We aimed to assess the distribution of transcription factor 7-like 2 gene TCF7L2 (rs7903146) polymorphism and to find possible associations between TCF7L2 and the characteristics of type 1 diabetes.

Materials and methods: We studied 190 newly diagnosed type 1 diabetes patients (median age 12.7 years, range 2.0-72.5) and 246 controls (median age 23.8 years, range 1.4-81.5) for TCF7L2 single nucleotide polymorphism. We determined anti-islet autoantibodies, random C-peptide levels, diabetes associated HLA DR/DQ haplotypes and genotypes in all patients.

Results: There were no differences in the distribution of TCF7L2 single nucleotide polymorphism between patients and controls. However, patients with in type 1 diabetes, after adjusting for age and sex, subjects carrying C allele were at risk for a C-peptide level lower than 0.5 nmol/L (OR 5.65 [95% CI: 1.14-27.92]) and for zinc transporter 8 autoantibody positivity (5.22 [1.34-20.24]). Participants without T allele were associated with a higher level of islet antigen-2 autoantibodies (3.51 [1.49-8.27]) and zinc transporter 8 autoantibodies (2.39 [1.14-4.99]).

Conclusions: The connection of TCF7L2 polymorphism with zinc transporter 8 and islet antigen-2 autoantibodies and C-peptide levels in patients supports the viewpoint that TCF7L2 is associated with the clinical signs and autoimmune characteristics of type 1 diabetes. The mechanisms of the interaction between the TCF7L2 risk genotype and anti-islet autoantibodies need to be studied further.

Keywords: Anti-islet autoantibodies; Transcription factor 7-like 2 gene; Type 1 diabetes.

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Autoantibodies
  • C-Peptide
  • Child
  • Child, Preschool
  • Diabetes Mellitus, Type 1* / genetics
  • Diabetes Mellitus, Type 2* / genetics
  • Genetic Predisposition to Disease
  • Genotype
  • Humans
  • Middle Aged
  • Polymorphism, Single Nucleotide
  • T Cell Transcription Factor 1 / genetics
  • Young Adult
  • Zinc Transporter 8 / genetics

Substances

  • Zinc Transporter 8
  • T Cell Transcription Factor 1
  • C-Peptide
  • Autoantibodies