title: The role of base excision repair in the development of primary open angle glaucoma in the Polish population.
abstract: Glaucoma is a leading cause of irreversible blindness in developing countries. Previous data have shown that progressive loss of human TM cells may be connected with chronic exposure to oxidative stress. This hypothesis may suggest a role of the base excision repair (BER) pathway of oxidative DNA damage in primary open angle glaucoma (POAG) patients. The aim of our study was to evaluate an association of BER gene polymorphism with a risk of POAG. Moreover, an association of clinical parameters was examined including cup disk ratio (c/d), rim area (RA) and retinal nerve fiber layer (RNFL) with glaucoma progression according to BER gene polymorphisms. Our research included 412 patients with POAG and 454 healthy controls. Gene polymorphisms were analyzed by PCR-RFLP. Heidelberg Retinal Tomography (HRT) clinical parameters were also analyzed. The 399 Arg/Gln genotype of the XRCC1 gene (OR 1.38; 95% CI 1.02-1.89 p = 0.03) was associated with an increased risk of POAG occurrence. It was indicated that the 399 Gln/Gln XRCC1 genotype might increase the risk of POAG progression according to the c/d ratio (OR 1.67; 95% CI 1.07-2.61 P = 0.02) clinical parameter. Moreover, the association of VF factor with 148 Asp/Glu of APE1 genotype distribution and POAG progression (OR 2.25; 95% CI 1.30-3.89) was also found. Additionally, the analysis of the 324 Gln/His MUTYH polymorphism gene distribution in the patient group according to RNFL factor showed that it might decrease the progression of POAG (OR 0.47; 95% CI 0.30-0.82 P = 0.005). We suggest that the 399 Arg/Gln polymorphism of the XRCC1 gene may serve as a predictive risk factor of POAG.
authors.affiliation: Department of Clinical Chemistry and Biochemistry, Medical University of Lodz, Poland.
authors.forename: Magda
authors.initials: M
authors.lastname: Cuchra
authors.affiliation: Department of Clinical Chemistry and Biochemistry, Medical University of Lodz, Poland.
authors.forename: Lukasz
authors.initials: L
authors.lastname: Markiewicz
authors.affiliation: Department of Clinical Chemistry and Biochemistry, Medical University of Lodz, Poland.
authors.forename: Bartosz
authors.initials: B
authors.lastname: Mucha
authors.affiliation: The Abramson Family Cancer Research Institute, Department of Cancer Biology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA; Department of Biochemistry and Molecular Biology, Hollings Cancer Center, Medical University of South Carolina, Charleston, SC 29425, USA.
authors.forename: Dariusz
authors.initials: D
authors.lastname: Pytel
authors.affiliation: Department of Ophthalmology, Medical University of Warsaw, SPKSO Hospital, Warsaw, Poland.
authors.forename: Katarzyna
authors.initials: K
authors.lastname: Szymanek
authors.affiliation: Department of Medical Biochemistry, Medical University of Lodz, Lodz, Poland.
authors.forename: Janusz
authors.initials: J
authors.lastname: Szemraj
authors.affiliation: Department of Ophthalmology, Medical University of Warsaw, SPKSO Hospital, Warsaw, Poland.
authors.forename: Jerzy
authors.initials: J
authors.lastname: Szaflik
authors.affiliation: Department of Ophthalmology, Medical University of Warsaw, SPKSO Hospital, Warsaw, Poland.
authors.forename: Jacek P
authors.initials: JP
authors.lastname: Szaflik
authors.affiliation: Department of Clinical Chemistry and Biochemistry, Medical University of Lodz, Poland. Electronic address: ireneusz.majsterek@umed.lodz.pl.
authors.forename: Ireneusz
authors.initials: I
authors.lastname: Majsterek
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D020552:Comet Assay; D004260:DNA Repair; D004268:DNA-Binding Proteins / Q000235:genetics*; D018450:Disease Progression; D004843:Epistasis, Genetic; D005260:Female; D005838:Genotype; D005902:Glaucoma, Open-Angle / Q000453:epidemiology / Q000235:genetics* / Q000473:pathology; D006801:Humans; D008214:Lymphocytes / Q000737:chemistry; D008297:Male; D008875:Middle Aged; D009898:Optic Disk / Q000473:pathology; D018384:Oxidative Stress / Q000235:genetics; D011044:Poland / Q000453:epidemiology; D012150:Polymorphism, Restriction Fragment Length; D020641:Polymorphism, Single Nucleotide; D055351:Retinal Neurons / Q000473:pathology; D012307:Risk Factors; D014794:Visual Fields; 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
keywords: BER; Gene polymorphism; HRT; Oxidative DNA damage; Primary open angle glaucoma