Fuchs Endothelial Corneal Dystrophy: Strong Association with rs613872 Not Paralleled by Changes in Corneal Endothelial TCF4 mRNA Level

Biomed Res Int. 2015:2015:640234. doi: 10.1155/2015/640234. Epub 2015 Sep 16.

Abstract

Fuchs endothelial corneal dystrophy (FECD) is a common corneal endotheliopathy with a complex and heterogeneous genetic background. Different variants in the TCF4 gene have been strongly associated with the development of FECD. TCF4 encodes the E2-2 transcription factor but the link between the strong susceptibility locus and disease mechanism remains elusive. Here, we confirm a strong positive association between TCF4 single nucleotide polymorphism rs613872 and FECD in Polish patients (OR = 12.95, 95% CI: 8.63-19.42, χ (2) = 189.5, p < 0.0001). We show that TCF4 expression at the mRNA level in corneal endothelium (n = 63) does not differ significantly between individuals with a particular TCF4 genotype. It is also not altered in FECD patients as compared to control samples. The data suggest that changes in the transcript level containing constitutive TCF4 exon encoding the amino-terminal part of the protein seem not to contribute to disease pathogenesis. However, considering the strong association of TCF4 allelic variants with FECD, genotyping of TCF4 risk alleles may be important in the clinical practice.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Basic Helix-Loop-Helix Leucine Zipper Transcription Factors / genetics*
  • Basic Helix-Loop-Helix Leucine Zipper Transcription Factors / metabolism
  • Endothelium, Corneal / metabolism
  • Female
  • Fuchs' Endothelial Dystrophy / diagnosis*
  • Fuchs' Endothelial Dystrophy / genetics*
  • Genetic Markers / genetics
  • Humans
  • Male
  • Middle Aged
  • Mutation / genetics
  • Polymorphism, Single Nucleotide / genetics*
  • RNA, Messenger / genetics*
  • RNA, Messenger / metabolism*
  • Reproducibility of Results
  • Sensitivity and Specificity
  • Transcription Factor 4
  • Transcription Factors / genetics*
  • Transcription Factors / metabolism

Substances

  • Basic Helix-Loop-Helix Leucine Zipper Transcription Factors
  • Genetic Markers
  • RNA, Messenger
  • TCF4 protein, human
  • Transcription Factor 4
  • Transcription Factors