E2-2 protein and Fuchs's corneal dystrophy.
N Engl J Med
; 363(11): 1016-24, 2010 Sep 09.
Article
en En
| MEDLINE
| ID: mdl-20825314
ABSTRACT
BACKGROUND:
Fuchs's corneal dystrophy (FCD) is a leading cause of corneal transplantation and affects 5% of persons in the United States who are over the age of 40 years. Clinically visible deposits called guttae develop under the corneal endothelium in patients with FCD. A loss of endothelial cells and deposition of an abnormal extracellular matrix are observed microscopically. In advanced disease, the cornea swells and becomes cloudy because the remaining endothelial cells are not sufficient to keep the cornea dehydrated and clear. Although rare genetic variation that contributes to both early-onset and typical late-onset forms of FCD has been identified, to our knowledge, no common variants have been reported.METHODS:
We performed a genomewide association study and replicated the most significant observations in a second, independent group of subjects.RESULTS:
Alleles in the transcription factor 4 gene (TCF4), encoding a member of the E-protein family (E2-2), were associated with typical FCD (P=2.3x10(-26)). The association increased the odds of having FCD by a factor of 30 for persons with two copies of the disease variants (homozygotes) and discriminated between case subjects and control subjects with about 76% accuracy. At least two regions of the TCF4 locus were associated independently with FCD. Alleles in the gene encoding protein tyrosine phosphatase receptor type G (PTPRG) were associated with FCD (P=4.0x10(-7)), but the association did not reach genomewide significance.CONCLUSIONS:
Genetic variation in TCF4 contributes to the development of FCD. (Funded by the National Eye Institute and others.)
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Cromosomas Humanos Par 13
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Distrofia Endotelial de Fuchs
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Polimorfismo de Nucleótido Simple
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Factores de Transcripción TCF
Tipo de estudio:
Prognostic_studies
Límite:
Humans
Idioma:
En
Revista:
N Engl J Med
Año:
2010
Tipo del documento:
Article
País de afiliación:
Estados Unidos