Genetic and environmental influences on oxidative damage assessed in elderly Danish twins.
Genetic and environmental influences on oxidative damage assessed in elderly Danish twins.
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DOI：
10.1016/j.freeradbiomed.2011.02.017
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发表时间：
2011-06-01
影响因子：
7.4
通讯作者：
Poulsen, Henrik E.
中科院分区：
文献类型：
--
作者：
Broedbaek, Kasper;Ribel-Madsen, Rasmus;Henriksen, Trine;Weimann, Allan;Petersen, Morten;Andersen, Jon T.;Afzal, Shoaib;Hjelvang, Brian;Roberts, L. Jackson, II;Vaag, Allan;Poulsen, Pernille;Poulsen, Henrik E.
关键词：
此前的研究表明，氧化应激与人类多种疾病之间存在关联，包括癌症、心血管疾病、糖尿病和慢性呼吸道疾病。这种损害在多大程度上是由遗传和环境因素决定的尚不清楚。在一项针对 198 名老年双胞胎的经典双胞胎研究中，我们研究了遗传因素与环境因素对核酸氧化和脂质过氧化的影响。使用液相色谱-串联质谱法测量 8-氧代-7,8-二氢-2'-脱氧鸟苷 (8-oxodG)、8-氧代-7,8-二氢鸟苷 (8-oxoGuo) 和二去甲二氢 F2-异前列腺烷代谢物 (F2-IsoP-M) 的尿排泄量。环境对核酸氧化和脂质过氧化的影响占主导地位，遗传因素的影响很小，同卵双胞胎和异卵双胞胎之间的组内相关性没有差异，8-oxodG（rMZ = 0.55，rDZ = 0.47；P = 0.43），F2-IsoP-M（rMZ = 0.33，rDZ = 0.22；P）也没有差异。 = 0.42）也不是 8-oxoGuo（rMZ = 0.45，rDZ = 0.58；P = 0.21）。因此，氧化损伤的三个标志物的遗传力估计值较低（h2 = 0.17 – 0.22）。氧化应激的三种尿液标志物密切相关（r = 0.60 – 0.84）。总之，我们在大量老年丹麦双胞胎中证明，核酸和脂质的“全身”氧化损伤主要由潜在可改变的非遗传因素决定。
Previous studies have shown association between oxidative stress and various diseases in humans including cancer, cardiovascular disease, diabetes and chronic respiratory disease. To what extent this damage is determined by genetic and environmental factors is unknown. In a classical twin study with 198 elderly twins we examined the contribution 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) were measured using liquid chromatography-tandem mass spectrometry. The environmental influence on nucleic acid oxidation and lipid peroxidation was predominant leaving only little to influence from genetic factors, as evidenced by no differences in intraclass correlations between monozygotic and dizygotic 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 non-genetic factors.
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