Replication of the TCF4 Intronic variant in Late-onset fuchs corneal dystrophy and evidence of independence from the FCD2 locus

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Abstract

PURPOSE. Fuchs corneal dystrophy (FCD) is an autosomal dominant disease of the corneal endothelium with variable penetrance and expressivity. Recently, rs613872, an intronic variation of TCF4 associated with late-onset FCD, was reported. The present study was undertaken to examine this association in our cohort of FCD patients, to assess the significance of this finding, and to investigate the candidacy of TCF4 in the context of the mapped FCD2 locus. METHODS. The authors recruited 170 patients with late-onset FCD and 180 age-matched controls. Blood samples were collected, and genomic DNA was extracted. A panel of nine SNPs spanning the entire TCF4 locus was genotyped both on this cohort and on three previously reported FCD2-linked families. The association of an individual SNP with late-onset FCD was evaluated with the Fisher exact test, and the coding exons and exon-intron boundaries of TCF4 were sequenced in 96 affected persons. RESULTS. The risk allele G of rs613872 is associated significantly with late-onset FCD (odds ratio, 4.2; P = 4.28 × 10-15) and was present in male and female affected persons without any sex bias, replicating recent findings, though the authors found no apparent correlation with the severity of the disease phenotype. Moreover, the risk allele did not cosegregate with the disease phenotype in any of the three FCD2-linked families. The authors did not identify any pathogenic variants in the coding region of TCF4. CONCLUSIONS. The authors report the first independent replication of rs613872 conferring risk of late-onset FCD. Their data suggest that this risk factor is likely independent of the FCD2 locus, whose causality remains unknown.

Original languageEnglish (US)
Pages (from-to)2825-2829
Number of pages5
JournalInvestigative Ophthalmology and Visual Science
Volume52
Issue number5
DOIs
StatePublished - Apr 2011

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Fuchs' Endothelial Dystrophy
Single Nucleotide Polymorphism
Exons
Alleles
Phenotype
Sexism
Corneal Endothelium
Penetrance
Causality
Introns
Odds Ratio
DNA

ASJC Scopus subject areas

  • Ophthalmology
  • Sensory Systems
  • Cellular and Molecular Neuroscience

Cite this

@article{ab7ed4f521394155bf5cfdfa100bf258,
title = "Replication of the TCF4 Intronic variant in Late-onset fuchs corneal dystrophy and evidence of independence from the FCD2 locus",
abstract = "PURPOSE. Fuchs corneal dystrophy (FCD) is an autosomal dominant disease of the corneal endothelium with variable penetrance and expressivity. Recently, rs613872, an intronic variation of TCF4 associated with late-onset FCD, was reported. The present study was undertaken to examine this association in our cohort of FCD patients, to assess the significance of this finding, and to investigate the candidacy of TCF4 in the context of the mapped FCD2 locus. METHODS. The authors recruited 170 patients with late-onset FCD and 180 age-matched controls. Blood samples were collected, and genomic DNA was extracted. A panel of nine SNPs spanning the entire TCF4 locus was genotyped both on this cohort and on three previously reported FCD2-linked families. The association of an individual SNP with late-onset FCD was evaluated with the Fisher exact test, and the coding exons and exon-intron boundaries of TCF4 were sequenced in 96 affected persons. RESULTS. The risk allele G of rs613872 is associated significantly with late-onset FCD (odds ratio, 4.2; P = 4.28 × 10-15) and was present in male and female affected persons without any sex bias, replicating recent findings, though the authors found no apparent correlation with the severity of the disease phenotype. Moreover, the risk allele did not cosegregate with the disease phenotype in any of the three FCD2-linked families. The authors did not identify any pathogenic variants in the coding region of TCF4. CONCLUSIONS. The authors report the first independent replication of rs613872 conferring risk of late-onset FCD. Their data suggest that this risk factor is likely independent of the FCD2 locus, whose causality remains unknown.",
author = "Riazuddin, {Sheikh Amer} and Elyse McGlumphy and Yeo, {William S.} and Jiangxia Wang and Nicholas Katsanis and Gottsch, {John D}",
year = "2011",
month = "4",
doi = "10.1167/iovs.10-6497",
language = "English (US)",
volume = "52",
pages = "2825--2829",
journal = "Investigative Ophthalmology and Visual Science",
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publisher = "Association for Research in Vision and Ophthalmology Inc.",
number = "5",

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TY - JOUR

T1 - Replication of the TCF4 Intronic variant in Late-onset fuchs corneal dystrophy and evidence of independence from the FCD2 locus

AU - Riazuddin, Sheikh Amer

AU - McGlumphy, Elyse

AU - Yeo, William S.

AU - Wang, Jiangxia

AU - Katsanis, Nicholas

AU - Gottsch, John D

PY - 2011/4

Y1 - 2011/4

N2 - PURPOSE. Fuchs corneal dystrophy (FCD) is an autosomal dominant disease of the corneal endothelium with variable penetrance and expressivity. Recently, rs613872, an intronic variation of TCF4 associated with late-onset FCD, was reported. The present study was undertaken to examine this association in our cohort of FCD patients, to assess the significance of this finding, and to investigate the candidacy of TCF4 in the context of the mapped FCD2 locus. METHODS. The authors recruited 170 patients with late-onset FCD and 180 age-matched controls. Blood samples were collected, and genomic DNA was extracted. A panel of nine SNPs spanning the entire TCF4 locus was genotyped both on this cohort and on three previously reported FCD2-linked families. The association of an individual SNP with late-onset FCD was evaluated with the Fisher exact test, and the coding exons and exon-intron boundaries of TCF4 were sequenced in 96 affected persons. RESULTS. The risk allele G of rs613872 is associated significantly with late-onset FCD (odds ratio, 4.2; P = 4.28 × 10-15) and was present in male and female affected persons without any sex bias, replicating recent findings, though the authors found no apparent correlation with the severity of the disease phenotype. Moreover, the risk allele did not cosegregate with the disease phenotype in any of the three FCD2-linked families. The authors did not identify any pathogenic variants in the coding region of TCF4. CONCLUSIONS. The authors report the first independent replication of rs613872 conferring risk of late-onset FCD. Their data suggest that this risk factor is likely independent of the FCD2 locus, whose causality remains unknown.

AB - PURPOSE. Fuchs corneal dystrophy (FCD) is an autosomal dominant disease of the corneal endothelium with variable penetrance and expressivity. Recently, rs613872, an intronic variation of TCF4 associated with late-onset FCD, was reported. The present study was undertaken to examine this association in our cohort of FCD patients, to assess the significance of this finding, and to investigate the candidacy of TCF4 in the context of the mapped FCD2 locus. METHODS. The authors recruited 170 patients with late-onset FCD and 180 age-matched controls. Blood samples were collected, and genomic DNA was extracted. A panel of nine SNPs spanning the entire TCF4 locus was genotyped both on this cohort and on three previously reported FCD2-linked families. The association of an individual SNP with late-onset FCD was evaluated with the Fisher exact test, and the coding exons and exon-intron boundaries of TCF4 were sequenced in 96 affected persons. RESULTS. The risk allele G of rs613872 is associated significantly with late-onset FCD (odds ratio, 4.2; P = 4.28 × 10-15) and was present in male and female affected persons without any sex bias, replicating recent findings, though the authors found no apparent correlation with the severity of the disease phenotype. Moreover, the risk allele did not cosegregate with the disease phenotype in any of the three FCD2-linked families. The authors did not identify any pathogenic variants in the coding region of TCF4. CONCLUSIONS. The authors report the first independent replication of rs613872 conferring risk of late-onset FCD. Their data suggest that this risk factor is likely independent of the FCD2 locus, whose causality remains unknown.

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SN - 0146-0404

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