Haplotype-based association study of TCF7L2 gene variants with the development of diabetic retinopathy in an Iranian population

Ophthalmic Genet. 2024 Jun;45(3):226-232. doi: 10.1080/13816810.2024.2318611. Epub 2024 Mar 21.

Abstract

Background: Diabetic retinopathy (DR) is recognized as one of the most prevalent complications of diabetes and a major cause of morbidity. Transcription factor 7-like 2 (TCF7L2), a pivotal component in the Wnt-signaling pathway, plays a significant role in β-cell development, blood-glucose homeostasis, cell survival, cell migration, and cell proliferation. Thus, this study aimed to assess the association between TCF7L2 variants (rs7903146, rs11196205, and rs12255372) with DR in a population-based association study.

Materials and methods: DNA was extracted from whole blood of all subjects by salting-out procedure. Total 524 T2DM patients including 234 T2DM individuals without DR and 290 T2DM individuals with DR were genotyped by TaqMan assay technology. Clinical characteristics of subjects were conducted to evaluate the plausible association between TCF7L2 variants and DR with univariate linear regression analysis.

Results: Demographic analysis between case and control groups revealed significant differences in FBS, HbA1c, lipidemia, heart disease, and family history of T2DM (p < 0.05). No significant difference was observed in either genotypes distribution or allele frequency (p > 0.05) between T2DM individuals with and without DR in any models of inheritance. Genotype-phenotype association showed no significant association. Result of analysis indicated that HbAlc with adjusted OR of 1.8 (p < 0.0001) and first-degree relatives of family history with adjusted OR of 3.04 (p < 0.0001) were significantly associated with DR. Finally, haplotype analysis showed no noticeable association.

Conclusion: In conclusion, there was no significant genetic association between rs7903146, rs11196205, and rs12255372 with DR among T2DM Iranians; however, these variants may play unknown roles in other populations.

Keywords: Iranian population; TCF7L2; association study; diabetic retinopathy; polymorphism.

MeSH terms

  • Adult
  • Aged
  • Case-Control Studies
  • Diabetes Mellitus, Type 2* / complications
  • Diabetes Mellitus, Type 2* / genetics
  • Diabetic Retinopathy* / epidemiology
  • Diabetic Retinopathy* / genetics
  • Female
  • Gene Frequency*
  • Genetic Association Studies
  • Genetic Predisposition to Disease
  • Genotype
  • Genotyping Techniques
  • Haplotypes*
  • Humans
  • Iran / epidemiology
  • Male
  • Middle Aged
  • Polymorphism, Single Nucleotide*
  • Transcription Factor 7-Like 2 Protein* / genetics

Substances

  • Transcription Factor 7-Like 2 Protein
  • TCF7L2 protein, human