Genetic and environmental influences on oxidative damage assessed in elderly Danish twins

Kasper Broedbaek, Rasmus Ribel-Madsen, Trine Henriksen, Allan Weimann, Morten Petersen, Jon T Andersen, Shoaib Afzal, Brian Hjelvang, L Jackson Roberts, Allan Vaag, Pernille Poulsen, Henrik E Poulsen

25 Citations (Scopus)

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 (F 2-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 (rMZ = 0.55, rDZ = 0.47; P = 0.43), F2-IsoP-M (rMZ = 0.33, rDZ = 0.22; P = 0.42), nor 8-oxoGuo (rMZ = 0.45, rDZ = 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.

Original languageEnglish
JournalFree Radical Biology & Medicine
Volume50
Issue number11
Pages (from-to)1488-91
Number of pages4
ISSN0891-5849
DOIs
Publication statusPublished - 1 Jun 2011

Keywords

  • Aged
  • Aged, 80 and over
  • Biological Markers
  • DNA Damage
  • Denmark
  • Deoxyguanosine
  • Environmental Exposure
  • F2-Isoprostanes
  • Female
  • Guanosine
  • Humans
  • Lipid Peroxidation
  • Male
  • Middle Aged
  • Oxidation-Reduction
  • Oxidative Stress
  • Twins, Dizygotic
  • Twins, Monozygotic

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