Effect of Trinucleotide Repeat Expansion on the Expression of TCF4 mRNA in Fuchs' Endothelial Corneal Dystrophy
| Autor: | Makiko Nakahara, Kengo Yoshii, Noriko Koizumi, Ross A. Aleff, Takahiko Sato, Ursula Schlötzer-Schrehardt, Derek J. Blake, Michael P. Fautsch, Keith H. Baratz, Edward W. Highsmith, Ryosuke Hayashi, Malinda L. Butz, Naoki Okumura, Kei Tashiro, Yuya Komori, Eric D. Wieben, Masakazu Nakano, Theofilos Tourtas, Friedrich E. Kruse |
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| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Adult Male Corneal endothelium Endothelium Genotyping Techniques Corneal dystrophy Biology Real-Time Polymerase Chain Reaction Cornea 03 medical and health sciences Young Adult 0302 clinical medicine Transcription Factor 4 medicine Humans RNA Messenger Fuchs' endothelial corneal dystrophy Southern blot TCF4 Aged Aged 80 and over Fuchs' Endothelial Dystrophy Middle Aged medicine.disease Molecular biology eye diseases Blot Blotting Southern 030104 developmental biology Real-time polymerase chain reaction medicine.anatomical_structure Gene Expression Regulation Female Trinucleotide repeat expansion Trinucleotide Repeat Expansion 030217 neurology & neurosurgery trinucleotide repeat Microsatellite Repeats |
| Zdroj: | Investigative Ophthalmology & Visual Science |
| ISSN: | 1552-5783 0146-0404 |
| Popis: | Purpose: CTG trinucleotide repeat (TNR) expansion is frequently found in transcription factor 4 (TCF4) in Fuchs' endothelial corneal dystrophy (FECD), though the effect of TNR expansion on FECD pathophysiology remains unclear. The purpose of this study was to evaluate the effect of TNR expansion on TCF4 expression in corneal endothelium of patients with FECD. \ud\udMethods: Peripheral blood DNA and Descemet membrane with corneal endothelium were obtained from 203 German patients with FECD. The CTG TNR repeat length in TCF4 was determined by short tandem repeat (STR) assays and Southern blotting using genomic DNA. Genotyping of rs613872 in TCF4 was performed by PCR. TCF4 mRNA levels in corneal endothelium were evaluated by quantitative PCR using three different probes. Control corneal endothelial samples were obtained from 35 non-FECD subjects. \ud\udResults: The STR assay and Southern blotting showed that 162 of the 203 patients with FECD (80%) harbored CTG trinucleotide repeat lengths larger than 50. Quantitative PCR using all three probes demonstrated that TCF4 mRNA is significantly upregulated in the corneal endothelium of patients with FECD, regardless of the presence of TNR expansion. However, the length of the TNR tended to show a positive correlation with TCF4 expression level. No correlation was shown between the genotype of TCF4 SNP, rs613872, and the level of TCF4 expression. \ud\udConclusions: Our findings showed that TCF4 mRNA is upregulated in the corneal endothelium of patients with FECD. Further studies on the effects of TCF4 upregulation on corneal endothelial cell function will aid in understanding the pathophysiology of FECD. |
| Databáze: | OpenAIRE |
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