E2-2 Protein and Fuchs's Corneal Dystrophy

被引:224
作者
Baratz, Keith H. [2 ]
Tosakulwong, Nirubol [3 ]
Ryu, Euijung [3 ]
Brown, William L. [2 ]
Branham, Kari [4 ]
Chen, Wei [5 ]
Tran, Khoa D. [1 ]
Schmid-Kubista, Katharina E. [2 ]
Heckenlively, John R. [4 ]
Swaroop, Anand [6 ]
Abecasis, Goncalo [5 ]
Bailey, Kent R. [3 ]
Edwards, Albert O. [1 ]
机构
[1] Univ Oregon, Inst Mol Biol, Eugene, OR 97403 USA
[2] Mayo Clin, Dept Ophthalmol, Rochester, MN USA
[3] Mayo Clin, Dept Biomed Stat & Informat, Rochester, MN USA
[4] Univ Michigan, Dept Ophthalmol & Visual Sci, Ann Arbor, MI 48109 USA
[5] Univ Michigan, Dept Biostat, Ann Arbor, MI 48109 USA
[6] NEI, Bethesda, MD 20892 USA
基金
美国国家卫生研究院;
关键词
SNOWFLAKE VITREORETINAL DEGENERATION; TYROSINE-PHOSPHATASE-GAMMA; ENDOTHELIAL DYSTROPHY; MACULAR DEGENERATION; TRANSCRIPTION FACTOR; MISSENSE MUTATIONS; IN-SITU; LINKAGE; FAMILY; EXPRESSION;
D O I
10.1056/NEJMoa1007064
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
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.)
引用
收藏
页码:1016 / 1024
页数:9
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