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Association of rs613872 and Trinucleotide Repeat Expansion in the TCF4 Gene of German Patients with Fuchs Endothelial Corneal Dystrophy
- Source :
- Cornea
- Publication Year :
- 2019
-
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 (STR) assays and Southern blotting. The possible associations between TNR length and clinical parameters (age, sex, visual acuity, and central corneal thickness) were analyzed in 132 patients. RESULT: 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, while no non-FECD control 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 (P=2.93×10(−25)). No significant association was detected between clinical parameters and TNR length. 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.
- Subjects :
- Adult
Male
Adolescent
Genotype
Nonsense mutation
Single-nucleotide polymorphism
Biology
Polymorphism, Single Nucleotide
Article
03 medical and health sciences
Young Adult
0302 clinical medicine
Transcription Factor 4
Polymorphism (computer science)
SNP
Humans
Genetic Predisposition to Disease
Allele
Genotyping
Alleles
Aged
Aged, 80 and over
Fuchs' Endothelial Dystrophy
Middle Aged
Molecular biology
Ophthalmology
030221 ophthalmology & optometry
Female
Trinucleotide repeat expansion
Trinucleotide Repeat Expansion
030217 neurology & neurosurgery
Subjects
Details
- Language :
- English
- Database :
- OpenAIRE
- Journal :
- Cornea
- Accession number :
- edsair.doi.dedup.....3fa82dcdc4d1fafd8068161f1f7551ab