title: Variation in DNA Base Excision Repair Genes in Fuchs Endothelial Corneal Dystrophy.
abstract: BACKGROUND Fuchs endothelial corneal dystrophy (FECD) is a corneal disease characterized by abnormalities in the Descemet membrane and the corneal endothelium. The etiology of this disease is poorly understood. An increased level of oxidative DNA damage reported in FECD corneas suggests a role of DNA base excision repair (BER) genes in its pathogenesis. In this work, we searched for the association between variation of the PARP-1, NEIL1, POLG, and XRCC1 genes and FECD occurrence. MATERIAL AND METHODS This study was conducted on 250 FECD patients and 353 controls using polymerase chain reaction-restriction fragment length polymorphism, high-resolution melting analysis, and the TaqMan® SNP Genotyping Assay. RESULTS We observed that the A/A genotype and the A allele of the c.1196A>G polymorphism of the XRCC1 gene were positively correlated with an increased FECD occurrence, whereas the G allele had the opposite effect. A weak association between the C/G genotype of the g.46438521G>C polymorphism of the NEIL1 gene and an increased incidence of FECD was also detected. Haplotypes of both polymorphisms of the XRCC1 were associated with FECD occurrence. No association of the c.2285T>C, c.-1370T>A and c.580C>T polymorphisms of the PARP-1, POLG and XRCC1 genes, respectively, with FECD occurrence was observed. CONCLUSIONS Our results suggest that the c.1196A>G polymorphism in the XRCC1 gene may be an independent genetic risk factor for FECD.
authors.affiliation: Department of Molecular Genetics, University of Łódź, Łódź, Poland.
authors.forename: Katarzyna A
authors.initials: KA
authors.lastname: Wójcik
authors.affiliation: Department of Molecular Genetics, University of Łódź, Łódź, Poland.
authors.forename: Ewelina
authors.initials: E
authors.lastname: Synowiec
authors.affiliation: Department of Ophthalmology, Medical University of Warsaw, Warsaw, Poland.
authors.forename: Piotr
authors.initials: P
authors.lastname: Polakowski
authors.affiliation: Department of Molecular Genetics, University of Łódź, Łódź, Poland.
authors.forename: Janusz
authors.initials: J
authors.lastname: Błasiak
authors.affiliation: Department of Ophthalmology, Medical University of Warsaw, Warsaw, Poland.
authors.forename: Jerzy
authors.initials: J
authors.lastname: Szaflik
authors.affiliation: Department of Ophthalmology, Medical University of Warsaw, Warszawa, Poland.
authors.forename: Jacek P
authors.initials: JP
authors.lastname: Szaflik
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D016022:Case-Control Studies; D045647:DNA Glycosylases / Q000235:genetics; D000074002:DNA Polymerase gamma; D004260:DNA Repair; D004268:DNA-Binding Proteins / Q000235:genetics; D004259:DNA-Directed DNA Polymerase / Q000235:genetics; D005260:Female; D005642:Fuchs' Endothelial Dystrophy / Q000235:genetics*; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D000071137:Poly (ADP-Ribose) Polymerase-1; D011065:Poly(ADP-ribose) Polymerases / Q000235:genetics; D020641:Polymorphism, Single Nucleotide; D017422:Sequence Analysis, DNA; D000076105:X-ray Repair Cross Complementing Protein 1
chemical_list: D004268:DNA-Binding Proteins; D000076105:X-ray Repair Cross Complementing Protein 1; C000619371:XRCC1 protein, human; C499320:PARP1 protein, human; D000071137:Poly (ADP-Ribose) Polymerase-1; D011065:Poly(ADP-ribose) Polymerases; D000074002:DNA Polymerase gamma; D004259:DNA-Directed DNA Polymerase; C413027:POLG protein, human; D045647:DNA Glycosylases; C473634:NEIL1 protein, human