title: Genetic variants in the DNA repair gene NEIL3 and the risk of myocardial infarction in a nested case-control study. The HUNT Study.
abstract: BACKGROUND
  Enhanced generation of reactive oxygen species and increased oxidative-induced DNA damage have been identified as possible contributors to atherosclerosis. The base excision repair (BER) pathway is the principal mechanism by which mammalian cells repair oxidative DNA damage. BER deficiency can potentially accelerate atherogenesis.
  
  
  METHODS
  We evaluated the association of Single Nucleotide Polymorphisms (SNPs) in genes encoding four different BER proteins (NEIL3, OGG1, APEX1 and XRCC1) with the incidence of myocardial infarction in a nested case-control study among participants of the second survey of the HUNT Study. The study population included 1624 cases and 4087 age- and sex-matched controls.
  
  
  RESULTS
  For the NEIL3 SNP rs12645561, the TT genotype was associated with increased risk of MI (OR 1.47, 95% CI 1.02-2.12, p uncorrected for multiple comparisons = 0.04) both in the genotypic test (compared to the CC genotype) and in the recessive genetic model (compared to the CC and CT genotypes combined). For the other two NEIL3 SNPs (rs10013040 and rs1395479) and for the SNPs of OGG1 (rs1052133), APEX1 (rs1878703) and XRCC1 (rs25489) we observed no association with risk of myocardial infarction.
  
  
  CONCLUSIONS
  We found that the NEIL3 rs12645561 SNP TT genotype was associated with increased risk of myocardial infarction. If confirmed in other studies, this association may suggest a possible role of attenuated DNA repair, and NEIL3 in particular, in atherogenesis.
authors.affiliation: Research Institute of Internal Medicine, Oslo University Hospital Rikshospitalet, Norway; Institute of Clinical Medicine, University of Oslo, 0424 Oslo, Norway. Electronic address: Tonje.Skarpengland@rr-research.no.
authors.forename: Tonje
authors.initials: T
authors.lastname: Skarpengland
authors.affiliation: Department of Public Health and General Practice, Norwegian University of Science and Technology, Norway.
authors.forename: Lars Erik
authors.initials: LE
authors.lastname: Laugsand
authors.affiliation: Department of Public Health and General Practice, Norwegian University of Science and Technology, Norway; Department of Public Health Sciences, Karolinska Institute, 171 77 Stockholm, Sweden.
authors.forename: Imre
authors.initials: I
authors.lastname: Janszky
authors.affiliation: Department of Microbiology, Oslo University Hospital Rikshospitalet, Norway.
authors.forename: Luisa
authors.initials: L
authors.lastname: Luna
authors.affiliation: Research Institute of Internal Medicine, Oslo University Hospital Rikshospitalet, Norway; Institute of Clinical Medicine, University of Oslo, 0424 Oslo, Norway; K.G. Jebsen Inflammatory Research Center, University of Oslo, 0424 Oslo, Norway.
authors.forename: Bente
authors.initials: B
authors.lastname: Halvorsen
authors.affiliation: Department of Medicine, Levanger Hospital, Nord-Trøndelag Hospital Trust, 7600 Levanger, Norway.
authors.forename: Carl G P
authors.initials: CG
authors.lastname: Platou
authors.affiliation: Department of Medical Biochemistry, Oslo University Hospital Rikshospitalet, Norway; Department of Microbiology, Oslo University Hospital Rikshospitalet, Norway.
authors.forename: Wei
authors.initials: W
authors.lastname: Wang
authors.affiliation: Department of Public Health and General Practice, Norwegian University of Science and Technology, Norway; Department of Epidemiology, Harvard School of Public Health, Boston, MA 02115, USA.
authors.forename: Lars J
authors.initials: LJ
authors.lastname: Vatten
authors.affiliation: Centre of Molecular Inflammation Research, Department of Cancer Research and Molecular Medicine, Norwegian University of Science and Technology, Norway; Department of Infectious Disease, St. Olavs Hospital, 7030 Trondheim, Norway.
authors.forename: Jan Kristian
authors.initials: JK
authors.lastname: Damås
authors.affiliation: Research Institute of Internal Medicine, Oslo University Hospital Rikshospitalet, Norway; Section of Clinical Immunology and Infectious Diseases, Oslo University Hospital Rikshospitalet, Norway; Institute of Clinical Medicine, University of Oslo, 0424 Oslo, Norway; K.G. Jebsen Inflammatory Research Center, University of Oslo, 0424 Oslo, Norway.
authors.forename: Pål
authors.initials: P
authors.lastname: Aukrust
authors.affiliation: Department of Medical Biochemistry, Oslo University Hospital Rikshospitalet, Norway; Department of Microbiology, Oslo University Hospital Rikshospitalet, Norway; Institute of Basic Medical Research, University of Oslo, 0424 Oslo, Norway.
authors.forename: Magnar
authors.initials: M
authors.lastname: Bjørås
authors.affiliation: Department of Public Health and General Practice, Norwegian University of Science and Technology, Norway; Department of Endocrinology, St. Olavs Hospital, 7030 Trondheim, Norway.
authors.forename: Bjørn O
authors.initials: BO
authors.lastname: Åsvold
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D016022:Case-Control Studies; D045647:DNA Glycosylases / Q000235:genetics; D043603:DNA-(Apurinic or Apyrimidinic Site) Lyase / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000235:genetics*; D009699:N-Glycosyl Hydrolases / Q000235:genetics*; 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; D009699:N-Glycosyl Hydrolases; C468764:NEIL3 protein, human; C479058:oxoguanine glycosylase 1, human; C085108:APEX1 protein, human; D043603:DNA-(Apurinic or Apyrimidinic Site) Lyase
keywords: Atherosclerosis; DNA glycosylase; Myocardial infarction; NEIL3; SNP