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, W Edward Jr. Highsmith, Eric D Wieben, Michael P Fautsch, Keith Baratz, Yuya Komori, Emi Ueda, Makiko Nakahara, Julia Weller, Theofilos Tourtas, Ursula Schlötzer-Schrehardt, Friedrich Kruse, Noriko Koizumi

Research output: Contribution to journalArticle

Abstract

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). 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). 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
JournalCornea
Volume38
Issue number7
DOIs
StatePublished - Jul 1 2019

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Fuchs' Endothelial Dystrophy
Trinucleotide Repeat Expansion
Trinucleotide Repeats
Transcription Factors
Single Nucleotide Polymorphism
Genes
Alleles
Nonsense Codon
Southern Blotting
Microsatellite Repeats
Visual Acuity
Genotype
DNA

ASJC Scopus subject areas

  • Ophthalmology

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Association of rs613872 and Trinucleotide Repeat Expansion in the TCF4 Gene of German Patients With Fuchs Endothelial Corneal Dystrophy. / Okumura, Naoki; Hayashi, Ryousuke; Nakano, Masakazu; Tashiro, Kei; Yoshii, Kengo; Aleff, Ross; Butz, Malinda; Highsmith, W Edward Jr.; Wieben, Eric D; Fautsch, Michael P; Baratz, Keith; Komori, Yuya; Ueda, Emi; Nakahara, Makiko; Weller, Julia; Tourtas, Theofilos; Schlötzer-Schrehardt, Ursula; Kruse, Friedrich; Koizumi, Noriko.

In: Cornea, Vol. 38, No. 7, 01.07.2019, p. 799-805.

Research output: Contribution to journalArticle

Okumura, N, Hayashi, R, Nakano, M, Tashiro, K, Yoshii, K, Aleff, R, Butz, M, Highsmith, WEJ, Wieben, ED, Fautsch, MP, Baratz, K, Komori, Y, Ueda, E, Nakahara, M, Weller, J, Tourtas, T, Schlötzer-Schrehardt, U, Kruse, F & Koizumi, N 2019, 'Association of rs613872 and Trinucleotide Repeat Expansion in the TCF4 Gene of German Patients With Fuchs Endothelial Corneal Dystrophy', Cornea, vol. 38, no. 7, pp. 799-805. https://doi.org/10.1097/ICO.0000000000001952
Okumura, Naoki ; Hayashi, Ryousuke ; Nakano, Masakazu ; Tashiro, Kei ; Yoshii, Kengo ; Aleff, Ross ; Butz, Malinda ; Highsmith, W Edward Jr. ; Wieben, Eric D ; Fautsch, Michael P ; Baratz, Keith ; Komori, Yuya ; Ueda, Emi ; Nakahara, Makiko ; Weller, Julia ; Tourtas, Theofilos ; Schlötzer-Schrehardt, Ursula ; Kruse, Friedrich ; Koizumi, Noriko. / Association of rs613872 and Trinucleotide Repeat Expansion in the TCF4 Gene of German Patients With Fuchs Endothelial Corneal Dystrophy. In: Cornea. 2019 ; Vol. 38, No. 7. pp. 799-805.
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title = "Association of rs613872 and Trinucleotide Repeat Expansion in the TCF4 Gene of German Patients With Fuchs Endothelial Corneal Dystrophy",
abstract = "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). 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). 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.",
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TY - JOUR

T1 - Association of rs613872 and Trinucleotide Repeat Expansion in the TCF4 Gene of German Patients With Fuchs Endothelial Corneal Dystrophy

AU - Okumura, Naoki

AU - Hayashi, Ryousuke

AU - Nakano, Masakazu

AU - Tashiro, Kei

AU - Yoshii, Kengo

AU - Aleff, Ross

AU - Butz, Malinda

AU - Highsmith, W Edward Jr.

AU - Wieben, Eric D

AU - Fautsch, Michael P

AU - Baratz, Keith

AU - Komori, Yuya

AU - Ueda, Emi

AU - Nakahara, Makiko

AU - Weller, Julia

AU - Tourtas, Theofilos

AU - Schlötzer-Schrehardt, Ursula

AU - Kruse, Friedrich

AU - Koizumi, Noriko

PY - 2019/7/1

Y1 - 2019/7/1

N2 - 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). 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). 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.

AB - 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). 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). 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.

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