Role of the TCF4 Gene Intronic Variant in Normal Variation of Corneal Endothelium

Cornea. 2012 Feb;31(2):162-6. doi: 10.1097/ICO.0b013e318226155f.


Purpose: To identify early features of Fuchs endothelial dystrophy (FED) in carriers of the rs613872(G) transcription factor 4 gene (TCF4) aged 20 to 21 years.

Methods: Prospective cohort study of people aged 20 to 21 years previously enrolled in the Western Australia Pregnancy (Raine) Cohort. Specular microscopy was performed using a noncontact specular microscopy (EM-3000; Tomey, Nagoya, Japan). Individual genotype data were extracted from the genome-wide Illumina 660 Quad Array. Analysis of the association between the rs613872 risk allele in TCF4 and specular microscopic measurements was conducted.

Results: Association between the rs613872 risk allele and corneal endothelial cell density (CD) as well as the coefficient of variation in cell shape was the main outcome measure. Genotype and specular microscopic data were available for a total of 445 participants (46% women). The median CD was 2851 and 2850 cells per square millimeter in the right and left eyes, respectively. No significant differences between intereye variability in endothelial CD were seen (right eye to left eye correlation = 0.64); however, a significant difference in variability of endothelial CD between men and women was observed (male: OD, 2839 ± 124 cells/mm² and OS, 2845 ± 124 cells/mm² vs. female: OD, 2838 ± 134 cells/mm² and OS, 2842 ± 132 cells/mm²; OD, P = 0.0013 and OS, P = 0.0016). Eleven individuals were homozygous for the rs613872 risk allele. We found no association between rs613872 genotype and CD or coefficient of variation. One of 11 homozygous GG individuals was found to have a gutta in 1 sample field on specular microscopy, whereas 2 of 297 TT individuals also had a gutta each in 1 sample field.

Conclusions: We were unable to detect an association between TCF4 rs613872 genotype and the variation in corneal endothelial CD or variation in cell morphology in a healthy young adult population.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alleles
  • Basic Helix-Loop-Helix Leucine Zipper Transcription Factors / genetics*
  • Cohort Studies
  • Epithelium, Corneal / cytology*
  • Female
  • Fuchs' Endothelial Dystrophy / genetics*
  • Genetic Variation / genetics
  • Genotype
  • Humans
  • Introns / genetics
  • Male
  • Prospective Studies
  • Transcription Factor 4
  • Transcription Factors / genetics*
  • Young Adult


  • Basic Helix-Loop-Helix Leucine Zipper Transcription Factors
  • TCF4 protein, human
  • Transcription Factor 4
  • Transcription Factors