title: CTG18.1 Expansion in TCF4 Increases Likelihood of Transplantation in Fuchs Corneal Dystrophy.
abstract: OBJECTIVE
  Fuchs dystrophy is the leading indication of corneal transplantation in the United States. A CTG18.1 trinucleotide repeat in TCF4 correlates with increased severity in Fuchs dystrophy; however, quantitative estimates of increased transplantation risk, including effects of age and sex, are unclear.
  
  
  METHODS
  In a tertiary institution clinical practice, 574 participants were enrolled in a longitudinal study of Fuchs dystrophy after slit-lamp biomicroscopy confirmed significant central guttae and/or corneal transplantation in both eyes. We documented clinical history, examination findings, and demographic information. We acquired blood samples, extracted DNA, and sequenced the CTG18.1 trinucleotide repeat in TCF4. In this retrospective case-control study, the number of participants with triplet expansion, defined as greater than 40 CTG repeats, and transplantation status were assessed. Kaplan-Meier estimates of timing and transplantation events were produced. The Cox proportional hazard regression model was used to assess the relationship between age, sex, triplet expansion, and surgery.
  
  
  RESULTS
  A total of 106 participants (18.5%) previously underwent corneal transplantation in at least 1 eye at the time of initial evaluation. A higher proportion of individuals harboring allele expansion had undergone transplantation (78/357, 21.8%) compared with those without the expanded allele (28/217, 12.9%), a significant association (P = 0.007). The log-rank test demonstrates a significant difference in survival function over time (P = 0.027), with a hazard ratio of 1.64 (95% confidence interval, 1.05-2.55).
  
  
  CONCLUSIONS
  Expansion of the TCF4 CTG trinucleotide repeat was associated with 1.64 times higher likelihood of corneal transplantation at a given age in patients with Fuchs dystrophy.
authors.affiliation: *Department of Ophthalmology, Johns Hopkins University School of Medicine, Baltimore, MD; and †Department of Biostatistics, Johns Hopkins University School of Public Health, Baltimore, MD.
authors.forename: Allen O
authors.initials: AO
authors.lastname: Eghrari
authors.forename: Shivakumar
authors.initials: S
authors.lastname: Vasanth
authors.forename: Jiangxia
authors.initials: J
authors.lastname: Wang
authors.forename: Farnoosh
authors.initials: F
authors.lastname: Vahedi
authors.forename: S Amer
authors.initials: SA
authors.lastname: Riazuddin
authors.forename: John D
authors.initials: JD
authors.lastname: Gottsch
mesh_terms: D000328:Adult; D000368:Aged; D000483:Alleles; D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors / Q000235:genetics*; D016022:Case-Control Studies; D016039:Corneal Transplantation / Q000706:statistics & numerical data*; D005260:Female; D005642:Fuchs' Endothelial Dystrophy / Q000235:genetics* / Q000601:surgery; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D016016:Proportional Hazards Models; D012189:Retrospective Studies; D000073940:Transcription Factor 4; D014157:Transcription Factors / Q000235:genetics*; D018911:Trinucleotide Repeats; D014481:United States
chemical_list: D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors; C532096:TCF4 protein, human; D000073940:Transcription Factor 4; D014157:Transcription Factors