title: Associations between DNA Damage, DNA Base Excision Repair Gene Variability and Alzheimer's Disease Risk.
abstract: Increased oxidative damage to DNA is one of the pathways involved in Alzheimer's disease (AD). Insufficient base excision repair (BER) is in part responsible for increased oxidative DNA damage. The aim of the present study was to assess the effect of polymorphic variants of BER-involved genes and the peripheral markers of DNA damage and repair in patients with AD.
  
  
  
  Comet assays and TaqMan probes were used to assess DNA damage, BER efxFB01;ciency and polymorphic variants of 12 BER genes in blood samples from 105 AD patients and 130 controls. The DNA repair efficacy (DRE) was calculated according to a specific equation.
  
  
  
  The levels of endogenous and oxidative DNA damages were higher in AD patients than controls. The polymorphic variants of XRCC1 c.580C>T XRCC1 c.1196A>G and OGG1 c.977C>G are associated with increased DNA damage in AD.
  
  
  
  Our results show that oxidative stress and disturbances in DRE are particularly responsible for the elevated DNA lesions in AD. The results suggest that oxidative stress and disruption in DNA repair may contribute to increased DNA damage in AD patients and risk of this disease. In addition, disturbances in DRE may be associated with polymorphisms of OGG1 and XRCC1.
authors.affiliation: Department of Molecular Genetics, University of Lodz, Lodz, Poland.
authors.forename: Dominik
authors.initials: D
authors.lastname: Kwiatkowski
authors.forename: Piotr
authors.initials: P
authors.lastname: Czarny
authors.forename: Monika
authors.initials: M
authors.lastname: Toma
authors.forename: Natalia
authors.initials: N
authors.lastname: Jurkowska
authors.forename: Agnieszka
authors.initials: A
authors.lastname: Sliwinska
authors.forename: Jozef
authors.initials: J
authors.lastname: Drzewoski
authors.forename: Agnieszka
authors.initials: A
authors.lastname: Bachurska
authors.forename: Janusz
authors.initials: J
authors.lastname: Szemraj
authors.forename: Michael
authors.initials: M
authors.lastname: Maes
authors.forename: Michael
authors.initials: M
authors.lastname: Berk
authors.forename: Kuan-Pin
authors.initials: KP
authors.lastname: Su
authors.forename: Piotr
authors.initials: P
authors.lastname: Galecki
authors.forename: Tomasz
authors.initials: T
authors.lastname: Sliwinski
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000235:genetics*; D016022:Case-Control Studies; D004249:DNA Damage; D045647:DNA Glycosylases / Q000235:genetics*; D004260:DNA Repair; D004268:DNA-Binding Proteins / Q000235:genetics*; D005260:Female; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D018384:Oxidative Stress; D020641:Polymorphism, Single Nucleotide; 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; D045647:DNA Glycosylases; C479058:oxoguanine glycosylase 1, human