Oxidative stress and epigenetic mortality risk score

• Verfasst von: Gao, Xu [VerfasserIn]
• Verfasst von: Gao, Xin [VerfasserIn]
• Verfasst von: Schöttker, Ben [VerfasserIn]
• Verfasst von: Brenner, Hermann [VerfasserIn]
• Titel: Oxidative stress and epigenetic mortality risk score
• Titelzusatz: associations with all-cause mortality among elderly people
• Verf.angabe: Xu Gao, Xīn Gào, Yan Zhang, Bernd Holleczek, Ben Schöttker, Hermann Brenner
• E-Jahr: 2019
• Jahr: 15 February 2019
• Umfang: 12 S.
• Teil: volume:34
• Teil: year:2019
• Teil: number:5
• Teil: pages:451-462
• Teil: extent:12
• Fussnoten: Gesehen am 15.05.2019
• Titel Quelle: Enthalten in: European journal of epidemiology
• Ort Quelle: [Cham] : Springer Nature Switzerland AG, 1985
• Jahr Quelle: 2019
• Band/Heft Quelle: 34(2019), 5, Seite 451-462
• ISSN Quelle: 1573-7284
• DOI: doi:10.1007/s10654-019-00493-7
• Datenträger: Online-Ressource
• Sprache: eng
• Sach-SW: Aging
• Sach-SW: All-cause mortality
• Sach-SW: DNA methylation
• Sach-SW: Epigenetic epidemiology
• Sach-SW: Mortality risk score
• Sach-SW: Oxidative stress
• K10plus-PPN: 1665689692

Abstract

Oxidative stress (OS) has been found to be related to accelerated aging and many aging-related health outcomes. Recently, an epigenetic “mortality risk score” (MS) based on whole blood DNA methylation at 10 mortality-related CpG sites has been demonstrated to be associated with all-cause mortality. This study aimed to address the association between OS and MS, and to assess and compare their performance in the prediction of all-cause mortality. For 1448 participants aged 50-75 of the German ESTHER cohort study, the MS was derived from the DNA methylation profiles measured by Illumina HumanMethylation450K Beadchip and the levels of two urinary OS markers, 8-isoprostane (8-iso) and oxidized guanine/guanosine [including 8-hydroxy-2′-deoxyguanosine (8-oxo)], were measured by ELISA kits. Associations between OS markers and the MS were evaluated by linear and ordinal logistic regression models, and their associations with all-cause mortality were examined by Cox regression models. Both OS markers were associated with the MS at baseline. The 8-iso levels and MS, but not 8-oxo levels, were associated with all-cause mortality during a median follow-up of 15.1 years. Fully-adjusted hazard ratios (95% CI) were 1.56 (1.13-2.16) for the 4th quartile of 8-iso levels compared with the 1st, 1.71 (1.27-2.29) and 2.92 (2.03-4.18) for the moderate and high MS defined by 2-5 and > 5 CpG sites with aberrant methylation compared with a MS of 0-1, respectively. After controlling for 8-iso levels, the hazard ratios of MS remained essentially unchanged while the association of 8-iso levels with mortality was attenuated. This study demonstrates that OS is highly associated with the epigenetic MS, and the latter at the same time has a higher predictive value for all-cause mortality.