title: Association between Single-Nucleotide Polymorphisms of the hOGG1,NEIL1,APEX1, FEN1,LIG1, and LIG3 Genes and Alzheimer's Disease Risk.
abstract: BACKGROUND
  One of the factors that contribute to Alzheimer's disease (AD) is the DNA damage caused by oxidative stress and inflammation that occurs in nerve cells. It has been suggested that the risk of AD may be associated with an age-dependent reduction of the DNA repair efficiency. Base excision repair (BER) is, among other things, a main repair system of oxidative DNA damage. One of the reasons for the reduced efficiency of this system may be single-nucleotide polymorphisms (SNP) of the genes encoding its proteins.
  
  
  METHODS
  DNA for genotyping was obtained from the peripheral blood of 281 patients and 150 controls. In the present study, we evaluated the impact of 8 polymorphisms of 6 BER genes on the AD risk. We analyzed the following SNP: c.-468T>G and c.444T>G of APEX1, c.*50C>T and c.*83A>C of LIG3, c.977C>G of OGG1, c.*283C>G of NEIL1, c.-441G>A of FEN1, and c.-7C>T of LIG1.
  
  
  RESULTS
  We showed that the LIG1 c.-7C>T A/A and LIG3 c.*83A>C A/C variants increased, while the APEX1 c.444T>G G/T, LIG1 c.-7C>T G/, LIG3 c.*83A>C C/C variants reduced, the AD risk. We also evaluated the relation between gene-gene interactions and the AD risk. We showed that combinations of certain BER gene variants such as c.977C>G×c.*50C>T CC/CT, c.444T>G×c.*50C>T GG/CT, c.-468T>G×c.*50C>T GG/CT, c.-441G>Ac.*50C>T×c.*50C>T GG/CT, c.*83A>C× c.*50C>T CT/AC, and c.-7C>T×c.*50C>T CT/GG can substantially positively modulate the risk of AD.
  
  
  CONCLUSIONS
  In conclusion, we revealed that polymorphisms of BER genes may have a significant effect on the AD risk, and the presence of polymorphic variants may be an important marker for AD.
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: Anna
authors.initials: A
authors.lastname: Korycinska
authors.forename: Katarzyna
authors.initials: K
authors.lastname: Sowinska
authors.forename: Piotr
authors.initials: P
authors.lastname: Galecki
authors.forename: Agnieszka
authors.initials: A
authors.lastname: Bachurska
authors.forename: Anna
authors.initials: A
authors.lastname: Bielecka-Kowalska
authors.forename: Janusz
authors.initials: J
authors.lastname: Szemraj
authors.forename: Michael
authors.initials: M
authors.lastname: Maes
authors.forename: Tomasz
authors.initials: T
authors.lastname: Sliwinski
mesh_terms: D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000453:epidemiology / Q000235:genetics*; D045647:DNA Glycosylases / Q000235:genetics; D000072481:DNA Ligase ATP / Q000235:genetics; D011088:DNA Ligases / Q000235:genetics; D043603:DNA-(Apurinic or Apyrimidinic Site) Lyase / Q000235:genetics; D005260:Female; D045585:Flap Endonucleases / Q000235:genetics; D020022:Genetic Predisposition to Disease; D006239:Haplotypes; D006801:Humans; D008297:Male; D008875:Middle Aged; D000075223:Poly-ADP-Ribose Binding Proteins; D020641:Polymorphism, Single Nucleotide; D012306:Risk; D012737:Sex Factors; D029867:Xenopus Proteins
chemical_list: C000607892:LIG1 protein, human; D000075223:Poly-ADP-Ribose Binding Proteins; D029867:Xenopus Proteins; D045585:Flap Endonucleases; C468317:FEN1 protein, human; D045647:DNA Glycosylases; C473634:NEIL1 protein, human; C479058:oxoguanine glycosylase 1, human; C085108:APEX1 protein, human; D043603:DNA-(Apurinic or Apyrimidinic Site) Lyase; D011088:DNA Ligases; D000072481:DNA Ligase ATP; C000618816:DNA ligase III alpha protein, Xenopus; C000618817:LIG3 protein, human