title: Association of the 399Arg/Gln XRCC1, the 194 Arg/Trp XRCC1, the 326Ser/Cys OGG1, and the 324Gln/His MUTYH gene polymorphisms with clinical parameters and the risk for development of primary open-angle glaucoma.
abstract: BACKGROUND
  Numerous data have shown that progressive loss of human trabecular meshwork (TM) cells may be connected with oxidative stress. This hypothesis may suggest an association of base excision repair with the risk of primary open angle glaucoma development.
  
  
  OBJECTIVE
  The aim of this study was to evaluate the role of the 399Arg/Gln XRCC1, the 194 Arg/Trp XRCC1, the 326SerCys OGG1, and the 324Gln/His MUTYH gene polymorphisms with clinical parameters and the risk for development of POAG.
  
  
  METHODS
  Our research included 170 patients with POAG and 193 healthy controls. Gene polymorphisms were investigated by PCR-RFLP. The Heidelberg Retinal Tomography (HRT) clinical parameters were also analyzed.
  
  
  RESULTS
  The 399Arg/Gln genotype of the XRCC1 gene was associated with an increased risk for POAG (OR 2.50; 95% CI, 1.54-4.07, P=0.0002). The 399Gln/Gln XRCC1 genotype may increase the risk for POAG progression according to clinical parameters such as cup/disk ratio (c/d) (OR 1.93; 95% CI, 1-3.73, P=0.04) and Rim area (RA factor) (OR 3.88; 95% CI, 1.01-14.82, P=0.04). Moreover, an association was found of retinal nerve-fiber layer (RNFL factor) with the 399Arg/Gln XRCC1 genotype distribution and POAG progression (OR 2.46; 95% CI, 1.06-5.68, P=0.03). In contrast, analysis of the 324Gln/His MUTYH gene polymorphism distribution in the patient group according to RA factor showed that it may reduce the progression of POAG (OR 0.14; 95% CI, 0.02-0.89, P=0.05). Our current study demonstrates an association between the 326Ser/Cys OGG1 gene polymorphism and the 326Cys allele of the OGG1 gene, and progression of POAG. In addition, the presence of the 326His allele of the MUTYH gene may increase the risk for POAG progression, according to the VF parameter (OR 2.57; 95% CI, 1.47-4.57, P=0.0001).
  
  
  CONCLUSIONS
  We suggest that the 399Arg/Gln genotype and the 399Gln allele of the XRCC1 gene may be risk factors for POAG development. Moreover, we postulate that the 399 Arg/Gln XRCC1, the 326 Ser/Cys OGG1 and the 324 Gln/His MUTYH genes polymorphisms may be associated with progression of POAG.
authors.affiliation: Department of Ophthalmology II, Medical Faculty, Medical University of Warsaw, Poland.
authors.forename: Jacek P
authors.initials: JP
authors.lastname: Szaflik
authors.forename: Magda
authors.initials: M
authors.lastname: Cuchra
authors.forename: Karolina
authors.initials: K
authors.lastname: Przybylowska-Sygut
authors.forename: Lukasz
authors.initials: L
authors.lastname: Dziki
authors.forename: Anna K
authors.initials: AK
authors.lastname: Kurowska
authors.forename: Mira
authors.initials: M
authors.lastname: Gacek
authors.forename: Jozef
authors.initials: J
authors.lastname: Drzewoski
authors.forename: Jerzy
authors.initials: J
authors.lastname: Szaflik
authors.forename: Ireneusz
authors.initials: I
authors.lastname: Majsterek
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D019943:Amino Acid Substitution; D002318:Cardiovascular Diseases / Q000453:epidemiology; D003062:Codon / Q000235:genetics; D015897:Comorbidity; D045647:DNA Glycosylases / Q000235:genetics* / Q000502:physiology; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000502:physiology; D003930:Diabetic Retinopathy / Q000453:epidemiology; D018450:Disease Progression; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D005902:Glaucoma, Open-Angle / Q000453:epidemiology / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D020125:Mutation, Missense; D017354:Point Mutation; D020641:Polymorphism, Single Nucleotide; D012306:Risk; D012720:Severity of Illness Index; D012907:Smoking / Q000453:epidemiology; D000076105:X-ray Repair Cross Complementing Protein 1
chemical_list: D003062:Codon; D004268:DNA-Binding Proteins; D000076105:X-ray Repair Cross Complementing Protein 1; C000619371:XRCC1 protein, human; D045647:DNA Glycosylases; C061738:mutY adenine glycosylase; C479058:oxoguanine glycosylase 1, human