TY - JOUR
T1 - E2-2 protein and Fuchs's corneal dystrophy
AU - Baratz, Keith H.
AU - Tosakulwong, Nirubol
AU - Ryu, Euijung
AU - Brown, William L.
AU - Branham, Kari
AU - Chen, Wei
AU - Tran, Khoa D.
AU - Schmid-Kubista, Katharina E.
AU - Heckenlively, John R.
AU - Swaroop, Anand
AU - Abecasis, Goncalo
AU - Bailey, Kent R.
AU - Edwards, Albert O.
PY - 2010/9/9
Y1 - 2010/9/9
N2 - 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 = 2.3×10-26). 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 = 4.0×10-7), 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.).
AB - 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 = 2.3×10-26). 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 = 4.0×10-7), 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.).
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U2 - 10.1056/NEJMoa1007064
DO - 10.1056/NEJMoa1007064
M3 - Article
C2 - 20825314
AN - SCOPUS:77956521660
SN - 0028-4793
VL - 363
SP - 1016
EP - 1024
JO - New England Journal of Medicine
JF - New England Journal of Medicine
IS - 11
ER -