Tonje Skarpengland1, Lars Erik Laugsand2, Imre Janszky3, Luisa Luna4, Bente Halvorsen5, Carl G P Platou6, Wei Wang7, Lars J Vatten8, Jan Kristian Damås9, Pål Aukrust10, Magnar Bjørås11, Bjørn O Åsvold12. 1. 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. 2. Department of Public Health and General Practice, Norwegian University of Science and Technology, Norway. 3. 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. 4. Department of Microbiology, Oslo University Hospital Rikshospitalet, Norway. 5. 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. 6. Department of Medicine, Levanger Hospital, Nord-Trøndelag Hospital Trust, 7600 Levanger, Norway. 7. Department of Medical Biochemistry, Oslo University Hospital Rikshospitalet, Norway; Department of Microbiology, Oslo University Hospital Rikshospitalet, Norway. 8. 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. 9. 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. 10. 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. 11. 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. 12. Department of Public Health and General Practice, Norwegian University of Science and Technology, Norway; Department of Endocrinology, St. Olavs Hospital, 7030 Trondheim, Norway.
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. CONCLUSION: 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.
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. CONCLUSION: We found that the NEIL3rs12645561 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: Alyssa A Rodriguez; Jessica L Wojtaszek; Briana H Greer; Tuhin Haldar; Kent S Gates; R Scott Williams; Brandt F Eichman Journal: J Biol Chem Date: 2020-09-02 Impact factor: 5.157
Authors: Tonje Skarpengland; Sverre Holm; Katja Scheffler; Ida Gregersen; Tuva B Dahl; Rajikala Suganthan; Filip M Segers; Ingunn Østlie; Jeroen J T Otten; Luisa Luna; Daniel F J Ketelhuth; Anna M Lundberg; Christine G Neurauter; Gunn Hildrestrand; Mona Skjelland; Bodil Bjørndal; Asbjørn M Svardal; Per O Iversen; Ulf Hedin; Ståle Nygård; Ole K Olstad; Kirsten Krohg-Sørensen; Geir Slupphaug; Lars Eide; Anna Kuśnierczyk; Lasse Folkersen; Thor Ueland; Rolf K Berge; Göran K Hansson; Erik A L Biessen; Bente Halvorsen; Magnar Bjørås; Pål Aukrust Journal: Sci Rep Date: 2016-06-22 Impact factor: 4.379
Authors: Wei He; Peng Huang; Dinghua Liu; Lingling Zhong; Rongbin Yu; Jianan Li Journal: Int J Environ Res Public Health Date: 2016-10-17 Impact factor: 3.390
Authors: Tom Rune Karlsen; Xiang Yi Kong; Sverre Holm; Ana Quiles-Jiménez; Tuva B Dahl; Kuan Yang; Ellen L Sagen; Tonje Skarpengland; Jonas D S Øgaard; Kristian Holm; Beate Vestad; Maria B Olsen; Pål Aukrust; Magnar Bjørås; Johannes R Hov; Bente Halvorsen; Ida Gregersen Journal: Sci Rep Date: 2021-10-05 Impact factor: 4.379