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, Edward W.
AU - Wieben, Eric D.
AU - Fautsch, Michael P.
AU - Baratz, Keith H.
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
N1 - Publisher Copyright:
© 2019 Wolters Kluwer Health, Inc. All rights reserved.
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 × 10-12). 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.
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 × 10-12). 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.
KW - Fuchs endothelial corneal dystrophy
KW - SNP
KW - TCF4
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U2 - 10.1097/ICO.0000000000001952
DO - 10.1097/ICO.0000000000001952
M3 - Article
C2 - 30973406
AN - SCOPUS:85067377092
SN - 0277-3740
VL - 38
SP - 799
EP - 805
JO - Cornea
JF - Cornea
IS - 7
ER -