TY - JOUR

T1 - Genetic and environmental influences on oxidative damage assessed in elderly Danish twins

AU - Broedbaek, Kasper

AU - Ribel-Madsen, Rasmus

AU - Henriksen, Trine

AU - Weimann, Allan

AU - Petersen, Morten

AU - Andersen, Jon T

AU - Afzal, Shoaib

AU - Hjelvang, Brian

AU - Roberts, L Jackson

AU - Vaag, Allan

AU - Poulsen, Pernille

AU - Poulsen, Henrik E

N1 - Copyright © 2011 Elsevier Inc. All rights reserved.

PY - 2011

Y1 - 2011

N2 - 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.

AB - 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.

KW - Aged

KW - Aged, 80 and over

KW - Biological Markers

KW - DNA Damage

KW - Denmark

KW - Deoxyguanosine

KW - Environmental Exposure

KW - F2-Isoprostanes

KW - Female

KW - Guanosine

KW - Humans

KW - Lipid Peroxidation

KW - Male

KW - Middle Aged

KW - Oxidation-Reduction

KW - Oxidative Stress

KW - Twins, Dizygotic

KW - Twins, Monozygotic

U2 - 10.1016/j.freeradbiomed.2011.02.017

DO - 10.1016/j.freeradbiomed.2011.02.017

M3 - Journal article

C2 - 21354303

VL - 50

SP - 1488

EP - 1491

JO - Free Radical Biology & Medicine

JF - Free Radical Biology & Medicine

SN - 0891-5849

IS - 11

ER -