title: Transethnic replication of association of CTG18.1 repeat expansion of TCF4 gene with Fuchs' corneal dystrophy in Chinese implies common causal variant.
abstract: OBJECTIVE
  To test the association between the CTG18.1 trinucleotide repeat expansion of TCF4 gene and Fuchs' endothelial corneal dystrophy (FECD) in a Chinese population.
  
  
  METHODS
  The trinucleotide repeat polymorphism CTG18.1 was genotyped using short tandem repeat and triplet repeat primed polymerase chain reaction assays in 57 Chinese subjects with FECD and 121 controls. Statistical association of the expanded CTG18.1 allele and 18 single nucleotide polymorphisms (SNPs) across TCF4 with FECD was evaluated. To investigate the linkage disequilibrium structure of the TCF4 region, haplotype analysis was performed on our study subjects and compared with genotyping data of 97 Han Chinese and 85 Caucasians in the 1000 Genomes Project.
  
  
  RESULTS
  The expanded CTG18.1 allele was associated with FECD (P = 4.7 × 10(-14)), with the odds ratio of each copy of the expanded allele estimated to be 66.5 (95% confidence interval: 12.6-350.1). Five TCF4 SNPs showed association with FECD at a nominal level (P < 5.0 × 10(-2)); however, conditional on the expanded CTG18.1 polymorphism, none of the SNPs showed association with FECD. The only haplotype associated with the disease was the one with the expansion at the CTG18.1 locus.
  
  
  CONCLUSIONS
  Transethnic replication of the association between the CTG18.1 repeat expansion in the TCF4 gene and FECD suggests it is a common, causal variant shared in Eurasian populations conferring significant risk for the development of FECD. Our data suggest that the expanded CTG18.1 allele is the main, if not sole, causal variant at this gene locus in the Chinese population.
authors.affiliation: University of Texas Southwestern Medical Center, McDermott Center for Human Growth and Development/Center for Human Genetics, Dallas, Texas, United States.
authors.forename: Chao
authors.initials: C
authors.lastname: Xing
authors.affiliation: University of Texas Southwestern Medical Center, Department of Ophthalmology, Dallas, Texas, United States.
authors.forename: Xin
authors.initials: X
authors.lastname: Gong
authors.affiliation: University of Texas Southwestern Medical Center, Department of Ophthalmology, Dallas, Texas, United States.
authors.forename: Imran
authors.initials: I
authors.lastname: Hussain
authors.affiliation: Division of Human Genetics, Genome Institute of Singapore, Singapore.
authors.forename: Chiea-Chuen
authors.initials: CC
authors.lastname: Khor
authors.affiliation: Singapore Eye Research Institute, Singapore.
authors.forename: Donald T H
authors.initials: DT
authors.lastname: Tan
authors.affiliation: Singapore Eye Research Institute, Singapore.
authors.forename: Tin
authors.initials: T
authors.lastname: Aung
authors.affiliation: Singapore Eye Research Institute, Singapore.
authors.forename: Jodhbir S
authors.initials: JS
authors.lastname: Mehta
authors.affiliation: Singapore Eye Research Institute, Singapore Department of Ophthalmology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore Department of Neuroscience, Duke-NUS Graduate Medical School, Singapore.
authors.forename: Eranga N
authors.initials: EN
authors.lastname: Vithana
authors.affiliation: University of Texas Southwestern Medical Center, McDermott Center for Human Growth and Development/Center for Human Genetics, Dallas, Texas, United States University of Texas Southwestern Medical Center, Department of Ophthalmology, Dallas, Texas, United States.
authors.forename: V Vinod
authors.initials: VV
authors.lastname: Mootha
mesh_terms: D000368:Aged; D000483:Alleles; D044466:Asian People / Q000235:genetics*; D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors / Q000235:genetics*; D004261:DNA Replication; D005260:Female; D005642:Fuchs' Endothelial Dystrophy / Q000208:ethnology / Q000235:genetics* / Q000473:pathology; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D015994:Incidence; D015810:Linkage Disequilibrium; D008297:Male; D018895:Microsatellite Repeats; D018613:Microscopy, Confocal; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D012846:Singapore / Q000208:ethnology; D000073940:Transcription Factor 4; D014157:Transcription Factors / Q000235:genetics*; D019680:Trinucleotide Repeat Expansion; D014481:United States / Q000453:epidemiology
chemical_list: D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors; C532096:TCF4 protein, human; D000073940:Transcription Factor 4; D014157:Transcription Factors
keywords: CTG18.1 trinucleotide repeat; Fuchs' corneal dystrophy; TCF4; genetic diseases