title: Polymorphisms of the apoptosis-related FAS and FAS ligand genes in keratoconus and Fuchs endothelial corneal dystrophy.
abstract: Keratoconus (KC) is a non-inflammatory eye disease characterized by progressive corneal thinning and asymmetrical conical protrusion of the cornea. Fuchs endothelial corneal dystrophy (FECD) is a degenerative, slowly progressive disease of the corneal endothelium that is characterized by alteration in corneal endothelial cell morphology and progressive loss of these cells. They are unrelated eye diseases that may ultimately lead to vision loss. Their pathogenesis is largely unknown, although impaired apoptosis has been suggested to be responsible for both diseases. Therefore, we studied the frequency of the c.-671A>G polymorphism of the apoptosis-related FAS gene and the c.-844T>C polymorphism of the FAS ligand (FASLG) gene in patients with FECD (221 individuals) or KC (264) and controls (300). Each polymorphism is located within the putative cis-acting element of the respective promoter. Risk of KC or FECD was estimated with unconditional multiple logistic regression with adjustment for various factors, including age, sex, allergies, and family history. The T/T genotype and the T allele of the c.-844T>C polymorphism were associated with increased occurrence of KC, while the C allele was associated with decreased KC occurrence. The G allele of the c.-671A>G polymorphism was associated with increased occurrence of FECD, while the A allele was associated with decreased FECD occurrence. The C/C-A/A combined genotype was associated with reduced risk of FECD, whereas the T/T-G/A combined genotype increased risk of KC. In conclusion, variability in the expression of the FAS and FASLG genes may be involved in the pathogenesis of KC and FECD.
authors.affiliation: Department of Molecular Genetics, University of Lodz.
authors.forename: Ewelina
authors.initials: E
authors.lastname: Synowiec
authors.forename: Katarzyna A
authors.initials: KA
authors.lastname: Wojcik
authors.forename: Justyna
authors.initials: J
authors.lastname: Izdebska
authors.forename: Janusz
authors.initials: J
authors.lastname: Blasiak
authors.forename: Jerzy
authors.initials: J
authors.lastname: Szaflik
authors.forename: Jacek P
authors.initials: JP
authors.lastname: Szaflik
mesh_terms: D017931:DNA Primers / Q000235:genetics; D053222:Fas Ligand Protein / Q000235:genetics*; D005642:Fuchs' Endothelial Dystrophy / Q000235:genetics*; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005838:Genotype; D006801:Humans; D007640:Keratoconus / Q000235:genetics*; D016015:Logistic Models; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D018570:Risk Assessment; D019014:fas Receptor / Q000235:genetics*
chemical_list: D017931:DNA Primers; C491901:FAS protein, human; C505661:FASLG protein, human; D053222:Fas Ligand Protein; D019014:fas Receptor