Association of rs613872 and Trinucleotide Repeat Expansion in the TCF4 Gene of German Patients with Fuchs Endothelial Corneal Dystrophy

Naoki Okumura, Ryousuke Hayashi, Masakazu Nakano, Kei Tashiro, Kengo Yoshii, Ross Aleff, Malinda Butz, Edward W. Highsmith, Eric D. Wieben, Michael P. Fautsch, Keith H. Baratz, Yuya Komori, Emi Ueda, Makiko Nakahara, Julia Weller, Theofilos Tourtas, Ursula Schlötzer-Schrehardt, Friedrich Kruse, Noriko Koizumi

Research output: Contribution to journalArticlepeer-review

2 Scopus citations


Purpose:To investigate single nucleotide polymorphisms (SNPs) and trinucleotide repeat (TNR) expansion in the transcription factor 4 (TCF4) gene in a large cohort of German patients with Fuchs endothelial corneal dystrophy (FECD).Methods:Genomic DNA was obtained from 398 patients with FECD and from 58 non-FECD controls. Thirty-seven previously reported SNPs were evaluated by genotyping. The 398 FECD samples were analyzed for TNR expansions by short tandem repeat assays and Southern blotting. The possible associations between the TNR length and clinical parameters (age, sex, visual acuity, and central corneal thickness) were analyzed in 132 patients.Results:The SNPs in COL8A2, TCF8, LOXHD1, and AGBL1 showed no heterogeneity in 36 cases, although SLCA411 showed 3 nonsense mutations. SNPs were detected for TCF4 (rs613872, rs2123392, rs17089887, rs1452787, and rs1348047), but only rs613872 showed a significant association with FECD (P = 9.93 × 10-12). Overall, 315/398 (79%) patients harbored TNR lengths >50, whereas no non-FECD controls harbored TNR lengths >50. The TCF4 SNP rs613872 genotype was TT: 39 (67%), TG: 18 (31%), and GG: 1 (2%) in non-FECD controls; TT: 39 (47%), TG: 38 (46%), and GG: 6 (7%) in FECD cases harboring TNR <50; and TT: 23 (8%), TG: 224 (79%), and GG: 38 (13%) in FECD cases harboring TNR >50 (P = 2.93 × 10-25). No significant association was detected between the TNR length and clinical parameters.Conclusions:Our large German cohort demonstrated a significant association between the risk allele G in rs613872 and FECD, irrespective of TNR expansion, although this risk allele was more frequent in FECD cases with TNR expansion than without.

Original languageEnglish (US)
Pages (from-to)799-805
Number of pages7
Issue number7
StatePublished - Jul 1 2019


  • Fuchs endothelial corneal dystrophy
  • SNP
  • TCF4

ASJC Scopus subject areas

  • Ophthalmology


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