Transethnic replication of association of CTG18.1 repeat expansion of TCF4 gene with fuchs’ corneal dystrophy in Chinese implies common causal variant

Chao Xing, Xin Gong, Imran Hussain, Chiea Chuen Khor, Donald T H Tan, Tin Aung, Jodhbir S. Mehta, Eranga N. Vithana, Venkateswara Mootha

Research output: Contribution to journalArticle

35 Scopus citations

Abstract

Purpose: 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) acrossTCF4 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.

Original languageEnglish (US)
Pages (from-to)7073-7078
Number of pages6
JournalInvestigative Ophthalmology and Visual Science
Volume55
Issue number11
DOIs
StatePublished - Oct 8 2014

Keywords

  • CTG18.1 trinucleotide repeat
  • Fuchs’ corneal dystrophy
  • Genetic diseases
  • TCF4

ASJC Scopus subject areas

  • Ophthalmology
  • Sensory Systems
  • Cellular and Molecular Neuroscience

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