title: Genetic and environmental influences on oxidative damage assessed in elderly Danish twins.
abstract: Previous studies have shown an association between oxidative stress and various diseases in humans including cancer, cardiovascular disease, diabetes, and chronic respiratory disease. To what extents this damage is determined by genetic and environmental factors is unknown. In a classical twin study with 198 elderly twins we examined the contributions of genetic versus environmental factors to nucleic acid oxidation and lipid peroxidation. Urinary excretion of 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG), 8-oxo-7,8-dihydroguanosine (8-oxoGuo), and dinor,dihydro F₂-isoprostane metabolites (F₂-IsoP-M) was measured using liquid chromatography-tandem mass spectrometry. The environmental influence on nucleic acid oxidation and lipid peroxidation was predominant, leaving only little influence from genetic factors, as evidenced by no differences in intraclass correlations between monozygotic (MZ) and dizygotic (DZ) twins, neither for 8-oxodG (r(MZ)=0.55, r(DZ)=0.47; P=0.43), F(2)-IsoP-M (r(MZ)=0.33, r(DZ)=0.22; P=0.42), nor 8-oxoGuo (r(MZ)=0.45, r(DZ)=0.58; P=0.21). Accordingly, heritability estimates for the three markers of oxidative damage were low (h²=0.17-0.22). The three urinary markers of oxidative stress were closely correlated (r=0.60-0.84). In conclusion, we demonstrated in a large population of elderly Danish twins that "whole-body" oxidative damage to nucleic acids and lipids is predominantly determined by potentially modifiable nongenetic factors.
authors.affiliation: Laboratory of Clinical Pharmacology Q7642, Rigshospitalet, DK-2200 Copenhagen, Denmark. kasper.broedbaek@rh.regionh.dk
authors.forename: Kasper
authors.initials: K
authors.lastname: Broedbaek
authors.forename: Rasmus
authors.initials: R
authors.lastname: Ribel-Madsen
authors.forename: Trine
authors.initials: T
authors.lastname: Henriksen
authors.forename: Allan
authors.initials: A
authors.lastname: Weimann
authors.forename: Morten
authors.initials: M
authors.lastname: Petersen
authors.forename: Jon T
authors.initials: JT
authors.lastname: Andersen
authors.forename: Shoaib
authors.initials: S
authors.lastname: Afzal
authors.forename: Brian
authors.initials: B
authors.lastname: Hjelvang
authors.forename: L Jackson
authors.initials: LJ
authors.lastname: Roberts
authors.forename: Allan
authors.initials: A
authors.lastname: Vaag
authors.forename: Pernille
authors.initials: P
authors.lastname: Poulsen
authors.forename: Henrik E
authors.initials: HE
authors.lastname: Poulsen
mesh_terms: D000080242:8-Hydroxy-2'-Deoxyguanosine; D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers / Q000652:urine; D004249:DNA Damage; D003718:Denmark; D003849:Deoxyguanosine / Q000031:analogs & derivatives / Q000652:urine; D004781:Environmental Exposure / Q000009:adverse effects; D028441:F2-Isoprostanes / Q000652:urine; D005260:Female; D006151:Guanosine / Q000031:analogs & derivatives / Q000652:urine; D006801:Humans; D015227:Lipid Peroxidation / Q000235:genetics; D008297:Male; D008875:Middle Aged; D010084:Oxidation-Reduction; D018384:Oxidative Stress / Q000235:genetics; D014429:Twins, Dizygotic / Q000235:genetics / Q000652:urine; D014430:Twins, Monozygotic / Q000235:genetics / Q000652:urine
chemical_list: D015415:Biomarkers; D028441:F2-Isoprostanes; D006151:Guanosine; C046215:8-hydroxyguanosine; D000080242:8-Hydroxy-2'-Deoxyguanosine; D003849:Deoxyguanosine