Study Links Genetic Variants to Fuchs's Corneal Dystrophy

Genetic variants in the TCF4 locus found to substantially increase risk for the disease

WEDNESDAY, Aug. 25 (HealthDay News) -- Researchers have identified genetic variants that substantially increase the risk for Fuchs's corneal dystrophy (FCD), and their research has been published online Aug. 25 by the New England Journal of Medicine.

Keith H. Baratz, M.D., of the Mayo Clinic in Rochester, Minn., and colleagues recruited 130 patients with FCD and 260 healthy controls and performed a genome-wide study to identify single-nucleotide polymorphisms (SNPs) associated with the condition. SNPs with the strongest association were then tested in a replication group of 150 patients, matched to 150 controls by age and sex.

The researchers found that alleles in the transcription factor 4 gene (TCF4), which encodes a member of the E-protein family, were associated with FCD (P = 2.3x10−26). Subjects with two copies of the variant (homozygotes) had a 30-fold increased FCD risk. Two or more regions of the TCF4 locus were independently linked to FCD. Also, alleles in the gene encoding protein tyrosine phosphatase receptor type G (PTPRG) exhibited an association with FCD (P = 4.0x10−7) that did not achieve genome-wide significance.

"In conclusion, our findings suggest that genetic variation in the TCF4 locus substantively contributes to the risk of FCD. The genetic risk appears to localize to multiple regions of the TCF4 locus. The prevalence of the risk haplotypes is relatively low (a few to several percent), but the presence of these haplotypes confers a high risk of FCD," the authors write.

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