title: Fuchs Endothelial Corneal Dystrophy: Strong Association with rs613872 Not Paralleled by Changes in Corneal Endothelial TCF4 mRNA Level.
abstract: Fuchs endothelial corneal dystrophy (FECD) is a common corneal endotheliopathy with a complex and heterogeneous genetic background. Different variants in the TCF4 gene have been strongly associated with the development of FECD. TCF4 encodes the E2-2 transcription factor but the link between the strong susceptibility locus and disease mechanism remains elusive. Here, we confirm a strong positive association between TCF4 single nucleotide polymorphism rs613872 and FECD in Polish patients (OR = 12.95, 95% CI: 8.63-19.42, χ (2) = 189.5, p < 0.0001). We show that TCF4 expression at the mRNA level in corneal endothelium (n = 63) does not differ significantly between individuals with a particular TCF4 genotype. It is also not altered in FECD patients as compared to control samples. The data suggest that changes in the transcript level containing constitutive TCF4 exon encoding the amino-terminal part of the protein seem not to contribute to disease pathogenesis. However, considering the strong association of TCF4 allelic variants with FECD, genotyping of TCF4 risk alleles may be important in the clinical practice.
authors.affiliation: Department of Genetics, World Hearing Center, Institute of Physiology and Pathology of Hearing, Warsaw, Poland ; Department of Histology and Embryology, Medical University of Warsaw, Warsaw, Poland.
authors.forename: Monika
authors.initials: M
authors.lastname: Ołdak
authors.affiliation: Department of Genetics, World Hearing Center, Institute of Physiology and Pathology of Hearing, Warsaw, Poland ; Department of Histology and Embryology, Medical University of Warsaw, Warsaw, Poland ; Postgraduate School of Molecular Medicine, Medical University of Warsaw, Warsaw, Poland.
authors.forename: Ewelina
authors.initials: E
authors.lastname: Ruszkowska
authors.affiliation: Department of Ophthalmology, Medical University of Warsaw, Warsaw, Poland.
authors.forename: Monika
authors.initials: M
authors.lastname: Udziela
authors.affiliation: Department of Genetics, World Hearing Center, Institute of Physiology and Pathology of Hearing, Warsaw, Poland.
authors.forename: Dominika
authors.initials: D
authors.lastname: Oziębło
authors.affiliation: Department of Ophthalmology, Medical University of Warsaw, Warsaw, Poland.
authors.forename: Ewelina
authors.initials: E
authors.lastname: Bińczyk
authors.affiliation: Department of Histology and Embryology, Medical University of Warsaw, Warsaw, Poland.
authors.forename: Aneta
authors.initials: A
authors.lastname: Ścieżyńska
authors.affiliation: Department of Medical Genetics, Medical University of Warsaw, Warsaw, Poland.
authors.forename: Rafał
authors.initials: R
authors.lastname: Płoski
authors.affiliation: Department of Ophthalmology, Medical University of Warsaw, Warsaw, Poland.
authors.forename: Jacek P
authors.initials: JP
authors.lastname: Szaflik
mesh_terms: D000328:Adult; D000368:Aged; D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors / Q000235:genetics* / Q000378:metabolism; D004728:Endothelium, Corneal / Q000378:metabolism; D005260:Female; D005642:Fuchs' Endothelial Dystrophy / Q000175:diagnosis* / Q000235:genetics*; D005819:Genetic Markers / Q000235:genetics; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics* / Q000378:metabolism*; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D000073940:Transcription Factor 4; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism
chemical_list: D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors; D005819:Genetic Markers; D012333:RNA, Messenger; C532096:TCF4 protein, human; D000073940:Transcription Factor 4; D014157:Transcription Factors