July 2018
Volume 59, Issue 9
Free
ARVO Annual Meeting Abstract  |   July 2018
Association of rs613872 and trinucleotide repeat expansion in the TCF4 gene in Fuchs endothelial corneal dystrophy in Germany
Author Affiliations & Notes
  • Yuya Komori
    Biomedical Engineering,Doshisha University, Kyotanabe, Kyoto, Japan
  • Naoki Okumura
    Biomedical Engineering,Doshisha University, Kyotanabe, Kyoto, Japan
  • Ryosuke Hayashi
    Biomedical Engineering,Doshisha University, Kyotanabe, Kyoto, Japan
  • Masakazu Nakano
    Genomic Medical Sciences,Kyoto Prefectural University of Medicine, Kyoto, Japan
  • Kei Tashiro
    Genomic Medical Sciences,Kyoto Prefectural University of Medicine, Kyoto, Japan
  • Kengo Yoshii
    Mathematics and Statistics in Medical Sciences,Kyoto Prefectural University of Medicine, Kyoto, Japan
  • Ross Aleff
    Biochemistry and Molecular Biology,Mayo Clinic, Rochester, Minnesota, United States
  • Malinda Butz
    Laboratory Medicine and Pathology,Mayo Clinic, Rochester, Minnesota, United States
  • Edward W. Highsmith
    Laboratory Medicine and Pathology,Mayo Clinic, Rochester, Minnesota, United States
  • Eric Wieben
    Biochemistry and Molecular Biology,Mayo Clinic, Rochester, Minnesota, United States
  • Michael P. Fautsch
    Ophthalmology,Mayo Clinic, Rochester, Minnesota, United States
  • Keith H Baratz
    Ophthalmology,Mayo Clinic, Rochester, Minnesota, United States
  • Theofilos Tourtas
    Ophthalmology, University of Erlangen-Nürnberg, Erlangen-Nuremberg, Germany
  • Ursula Schlotzer-Schrehardt
    Ophthalmology, University of Erlangen-Nürnberg, Erlangen-Nuremberg, Germany
  • Friedrich E Kruse
    Ophthalmology, University of Erlangen-Nürnberg, Erlangen-Nuremberg, Germany
  • Noriko Koizumi
    Biomedical Engineering,Doshisha University, Kyotanabe, Kyoto, Japan
  • Footnotes
    Commercial Relationships   Yuya Komori, None; Naoki Okumura, None; Ryosuke Hayashi, None; Masakazu Nakano, None; Kei Tashiro, None; Kengo Yoshii, None; Ross Aleff, None; Malinda Butz, None; Edward Highsmith, None; Eric Wieben, None; Michael Fautsch, None; Keith Baratz, None; Theofilos Tourtas, None; Ursula Schlotzer-Schrehardt, None; Friedrich Kruse, None; Noriko Koizumi, None
  • Footnotes
    Support  Program for the Strategic Reserch Foundation at Private Universities from MEXT (Koizumi N and Okumura N).
Investigative Ophthalmology & Visual Science July 2018, Vol.59, 1353. doi:
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      Yuya Komori, Naoki Okumura, Ryosuke Hayashi, Masakazu Nakano, Kei Tashiro, Kengo Yoshii, Ross Aleff, Malinda Butz, Edward W. Highsmith, Eric Wieben, Michael P. Fautsch, Keith H Baratz, Theofilos Tourtas, Ursula Schlotzer-Schrehardt, Friedrich E Kruse, Noriko Koizumi; Association of rs613872 and trinucleotide repeat expansion in the TCF4 gene in Fuchs endothelial corneal dystrophy in Germany. Invest. Ophthalmol. Vis. Sci. 2018;59(9):1353.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose : Single nucleotide polymorphisms (SNPs) in several genes have been associated with Fuchs endothelial corneal dystrophy (FECD). Among those SNPs, rs613872 in transcription factor 4 (TCF4) showed strong association, and accumulating evidence indicates that intronic CTG trinucleotide repeat expansion is frequently found in TCF4. The purpose of this study was to investigate SNPs and trinucleotide repeat expansion in TCF4 in the large cohort of German patients with FECD.

Methods : Genomic DNA was obtained from the peripheral blood of 398 German patients with FECD. The genomic DNA of 57 non-FECD controls was obtained from donor corneas of healthy individuals. Previously reported 37 SNPs in COL8A2, SLCA411, TCF8, LOXHD1, AGBL1, and TCF4 was evaluated in 36 randomly selected samples of FECD by genotyping. The expansion of a CTG trinucleotide repeat was analyzed by STR assay and Southern blotting in 398 FECD samples.

Results : No heterogeneity was found in SNPs in COL8A2, TCF8, LOXHD1 and AGBL1 in 36 cases, though 3 nonsense mutations were detected in SLCA411. In contrast, SNPs of TCF4; rs613872, rs2123392, rs17089887, rs1452787, and rs1348047 were detected. Only rs613872 showed significant association with FECD in comparison to non-FECD control (P<7.08×10-12). STR assay and Southern blotting demonstrated that 315 (homozygous 8, heterozygous 307) /398 patients (79.1%) harbored CTG trinucleotide repeat lengths > 50. Genotype of TCF4 SNP rs613872 was TT:38 (68%), TG:17 (30%), and GG:1 (2%) in non-FECD controls TT:39 (47%), TG: 38 (46%), and GG:6 (7%) in FECD harboring trinucleotide repeat lengths < 50, and TT:23 (7%), TG: 224 (71%), and GG:68 (22%) in FECD harboring trinucleotide repeat lengths > 50 (P<1.42×10-29).

Conclusions : CTG repeat expansion was found in 79% of German FECD patients, similar to the findings in other Caucasian cohorts. Among previously reported SNPs, only variation in rs613872 in TCF4 showed a strong correlation with FECD in this study group. Our large cohort demonstrated that risk allele G was associated with FECD with or without trinucleotide repeat expansion, though this risk allele was more frequently found in FECD harboring repeat expansion than in FECD without repeat expansion.

This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.

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