title: Polymorphism of the DNA base excision repair genes in keratoconus.
abstract: Keratoconus (KC) is a degenerative corneal disorder for which the exact pathogenesis is not yet known. Oxidative stress is reported to be associated with this disease. The stress may damage corneal biomolecules, including DNA, and such damage is primarily removed by base excision repair (BER). Variation in genes encoding BER components may influence the effectiveness of corneal cells to cope with oxidative stress. In the present work we genotyped 5 polymorphisms of 4 BER genes in 284 patients and 353 controls. The A/A genotype of the c.-1370T>A polymorphism of the DNA polymerase γ (POLG) gene was associated with increased occurrence of KC, while the A/T genotype was associated with decreased occurrence of KC. The A/G genotype and the A allele of the c.1196A>G polymorphism of the X-ray repair cross-complementing group 1 (XRCC1) were associated with increased, and the G/G genotype and the G allele, with decreased KC occurrence. Also, the C/T and T as well as C/C genotypes and alleles of the c.580C>T polymorphism of the same gene displayed relationship with KC occurrence. Neither the g.46438521G>C polymorphism of the Nei endonuclease VIII-like 1 (NEIL1) nor the c.2285T>C polymorphism of the poly(ADP-ribose) polymerase-1 (PARP-1) was associated with KC. In conclusion, the variability of the XRCC1 and POLG genes may play a role in KC pathogenesis and determine the risk of this disease.
authors.affiliation: Department of Molecular Genetics, University of Lodz, Pomorska 141/143, 90-236 Lodz, Poland. kwojcik@biol.uni.lodz.pl.
authors.forename: Katarzyna A
authors.initials: KA
authors.lastname: Wojcik
authors.affiliation: Department of Molecular Genetics, University of Lodz, Pomorska 141/143, 90-236 Lodz, Poland. ewelinas@biol.uni.lodz.pl.
authors.forename: Ewelina
authors.initials: E
authors.lastname: Synowiec
authors.affiliation: Department of Molecular Genetics, University of Lodz, Pomorska 141/143, 90-236 Lodz, Poland. katarzyna2781@wp.pl.
authors.forename: Katarzyna
authors.initials: K
authors.lastname: Sobierajczyk
authors.affiliation: Department of Ophthalmology, Medical University of Warsaw, SPKSO Ophthalmic Hospital, Sierakowskiego 13, 03-709 Warsaw, Poland. justyna_izdebska@yahoo.es.
authors.forename: Justyna
authors.initials: J
authors.lastname: Izdebska
authors.affiliation: Department of Molecular Genetics, University of Lodz, Pomorska 141/143, 90-236 Lodz, Poland. jblasiak@biol.uni.lodz.pl.
authors.forename: Janusz
authors.initials: J
authors.lastname: Blasiak
authors.affiliation: Department of Ophthalmology, Medical University of Warsaw, SPKSO Ophthalmic Hospital, Sierakowskiego 13, 03-709 Warsaw, Poland. szaflik@szaflik.pl.
authors.forename: Jerzy
authors.initials: J
authors.lastname: Szaflik
authors.affiliation: Department of Ophthalmology, Medical University of Warsaw, SPKSO Ophthalmic Hospital, Sierakowskiego 13, 03-709 Warsaw, Poland. szaflik@ophthalmology.pl.
authors.forename: Jacek P
authors.initials: JP
authors.lastname: Szaflik
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; 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; D004843:Epistasis, Genetic; D005260:Female; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D007640:Keratoconus / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D000071137:Poly (ADP-Ribose) Polymerase-1; D011065:Poly(ADP-ribose) Polymerases / Q000235:genetics; D011110:Polymorphism, Genetic; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors; D000076105:X-ray Repair Cross Complementing Protein 1; D055815:Young Adult
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