Association of<i>TCF4</i>Gene Polymorphisms with Fuchs' Corneal Dystrophy in the Chinese

Thalamuthu, Anbupalam; Khor, Chiea‐Chuen; Venkataraman, Divya; Koh, Li Wei; Tan, Donald; Aung, Tin; Mehta, Jodhbir S.; Vithana, Eranga N.

doi:10.1167/iovs.11-7568

Cited by 49 publications

(61 citation statements)

References 31 publications

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“…13 Similarly, ZEB1 (TCF8) first identified in posterior polymorphous corneal dystrophy, also contributes to a small proportion of FECD. 7 Genome-wide association study of late-onset sporadic FECD identified rs613872 in the intronic region of TCF4 gene to be significantly associated with the disease and also been replicated in various cohorts [14][15][16][17] (our cohort-data unpublished). Very recently, TGC trinucleotide repeat expansion in the intron of TCF4 gene has been identified to be associated with the disease and an expansion of 450 repeats being highly specific for the disease compared with the single-nucleotide polymorphism (SNP; rs613872).…”

Section: Introductionmentioning

confidence: 69%

Biosynthetic and functional defects in newly identified SLC4A11 mutants and absence of COL8A2 mutations in Fuchs endothelial corneal dystrophy

et al. 2014

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Late-onset Fuchs endothelial corneal dystrophy (FECD) shows genetic heterogeneity. Identification of SLC4A11 as a candidate gene for congenital hereditary endothelial dystrophy with similar corneal endothelial defects as FECD and reduced mRNA expression of SLC4A11 in the endothelium of FECD cases suggested that this gene may also be involved in pathogenesis of FECD. Mutations in SLC4A11 give rise to SLC4A11 protein marked by retention in the endoplasmic reticulum as a result of mis-folding. We screened 45 sporadic late-onset, 4 early-onset FECD patients and an early-onset autosomal dominant FECD family. We identified three previously unreported missense mutations: c.719G>C (p.W240S), c.1519G>A (p.V507I) and c.1304C>T (p.T434I) in unrelated individuals. These SLC4A11 mutants, expressed in HEK293 cells, had defects in either their cell surface expression or functional activity (rate of osmotically driven water flux). SLC4A11 mutations contribute to 11% (5/45) of sporadic late-onset FECD in the cohort studied. COL8A2, which causes some cases of early-onset FECD, was also screened in this cohort. No mutations were identified in COL8A2, in neither the late-onset cohort nor the early-onset family, suggesting genetic heterogeneity in this FECD family.

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Section: Introductionmentioning

confidence: 69%

Biosynthetic and functional defects in newly identified SLC4A11 mutants and absence of COL8A2 mutations in Fuchs endothelial corneal dystrophy

et al. 2014

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“…38 Globally, findings were replicated in an Australian cohort of 105 cases and 275 controls with odds ratio of 4.05. 39 In a Chinese cohort of 57 affected and 121 unaffected individuals, two other SNPs in TCF4 were significantly associated with FCD affectation with an odds ratio over 2 40 ; however, the rs613872 minor allele was absent among the affected cohort.…”

Section: Association Studiesmentioning

confidence: 99%

Fuchs Corneal Dystrophy

Eghrari

Riazuddin

Gottsch

2015

Progress in Molecular Biology and Translational Science

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“…19 In the same study, SNPs in the PTPRG (protein tyrosine phosphatase, receptor type, G) gene were nominally associated with FED, but the association did not reach genome-wide significance. Independent replication studies have confirmed association of TCF4 variants with late-onset FED in Caucasian American 20 and Chinese cohorts, 21 but the association with PTPRG remains to be confirmed.…”

Section: Introductionmentioning

confidence: 99%

Association of TCF4 and CLU polymorphisms with Fuchs’ endothelial dystrophy and implication of CLU and TGFBI proteins in the disease process

et al. 2012

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Fuchs' endothelial dystrophy (FED) is a disease affecting the corneal endothelium. Recent studies reported significant association of polymorphisms in the TCF4 (transcription factor 4) gene, and a borderline association of PTPRG (protein tyrosine phosphatase, receptor type, G) variants with late-onset FED in Caucasians from the United States. Association of TCF4 has also been reported in the Chinese population. We aimed to determine association of the reported polymorphisms in TCF4 and PTPRG, and association of polymorphisms in the candidate genes ZEB1 (zinc-finger E-box binding homoebox 1), COL8A2 (collagen, type VIII, alpha 2), TGFBI (transforming growth factor, b-induced) and CLU (clusterin) in Australian cases. We also compared the expression of TGFBI and CLU proteins between FED and normal whole corneas. In all, 30 single-nucleotide polymorphisms (SNPs) from the candidate genes were genotyped in 103 cases and 275 controls. Each SNP and haplotype was assessed for association with the disease. SNP analysis identified an association of TCF4 (rs613872 (P¼5.25Â10 À15 , OR¼4.05), rs9954153 (P¼3.37Â10 À7 , OR¼2.58), rs2286812 (P¼4.23Â10 À6 , OR¼2.55) and rs17595731 (P¼3.57Â10 À5 , OR¼3.79)), CLU (rs17466684; P¼0.003, OR¼1.85) and one haplotype of TGFBI SNPs (P¼0.011, OR¼2.29) with FED in Caucasian Australians. No evidence for genetic association of PTPRG, ZEB1 and COL8A2 was found. Immunohistochemistry showed differential expression of CLU and TGFBI proteins in FED-affected compared with normal corneas. In conclusion, variation in TCF4, CLU and TGFBI, but not PTPRG, ZEB1 and COL8A2 genes are associated with FED in Caucasian Australian cases. Differential expression of CLU and TGFBI proteins in FED-affected corneas provides novel insights into the disease mechanism.

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Association ofTCF4Gene Polymorphisms with Fuchs' Corneal Dystrophy in the Chinese

Abstract: Polymorphisms within TCF4, a gene which has been implicated in FCD susceptibility among Europeans, was also found to be strongly associated with FCD in Chinese.

Cited by 49 publications

References 31 publications

Biosynthetic and functional defects in newly identified SLC4A11 mutants and absence of COL8A2 mutations in Fuchs endothelial corneal dystrophy

Biosynthetic and functional defects in newly identified SLC4A11 mutants and absence of COL8A2 mutations in Fuchs endothelial corneal dystrophy

Fuchs Corneal Dystrophy

Association of TCF4 and CLU polymorphisms with Fuchs’ endothelial dystrophy and implication of CLU and TGFBI proteins in the disease process

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