Clinical epigenetics · 2019
Alzheimer's disease-associated (hydroxy)methylomic changes in the brain and blood.
Сравнительное исследованиеСтатьяПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод пока не подготовлен
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Lardenoije Roy, Roubroeks Janou A Y, Pishva Ehsan, Leber Markus, Wagner Holger, Iatrou Artemis, Smith Adam R, Smith Rebecca G, Eijssen Lars M T, Kleineidam Luca, Kawalia Amit, Hoffmann Per, Luck Tobias, Riedel-Heller Steffi, Jessen Frank, Maier Wolfgang, Wagner Michael, Hurlemann René, Kenis Gunter, Ali Muhammad, Del Sol Antonio, Mastroeni Diego, Delvaux Elaine, Coleman Paul D, Mill Jonathan, Rutten Bart P F, Lunnon Katie, Ramirez Alfredo, van den Hove Daniël L A
Аннотация
BACKGROUND: Late-onset Alzheimer's disease (AD) is a complex multifactorial affliction, the pathogenesis of which is thought to involve gene-environment interactions that might be captured in the epigenome. The present study investigated epigenome-wide patterns of DNA methylation (5-methylcytosine, 5mC) and hydroxymethylation (5-hydroxymethylcytosine, 5hmC), as well as the abundance of unmodified cytosine (UC), in relation to AD.
RESULTS: We identified epigenetic differences in AD patients (n = 45) as compared to age-matched controls (n = 35) in the middle temporal gyrus, pertaining to genomic regions close to or overlapping with genes such as OXT (- 3.76% 5mC, pŠidák = 1.07E-06), CHRNB1 (+ 1.46% 5hmC, pŠidák = 4.01E-04), RHBDF2 (- 3.45% UC, pŠidák = 4.85E-06), and C3 (- 1.20% UC, pŠidák = 1.57E-03). In parallel, in an independent cohort, we compared the blood methylome of converters to AD dementia (n = 54) and non-converters (n = 42), at a preclinical stage. DNA methylation in the same region of the OXT promoter as found in the brain was found to be associated with subsequent conversion to AD dementia in the blood of elderly, non-demented individuals (+ 3.43% 5mC, pŠidák = 7.14E-04).
CONCLUSIONS: The implication of genome-wide significant differential methylation of OXT, encoding oxytocin, in two independent cohorts indicates it is a promising target for future studies on early biomarkers and novel therapeutic strategies in AD.
RESULTS: We identified epigenetic differences in AD patients (n = 45) as compared to age-matched controls (n = 35) in the middle temporal gyrus, pertaining to genomic regions close to or overlapping with genes such as OXT (- 3.76% 5mC, pŠidák = 1.07E-06), CHRNB1 (+ 1.46% 5hmC, pŠidák = 4.01E-04), RHBDF2 (- 3.45% UC, pŠidák = 4.85E-06), and C3 (- 1.20% UC, pŠidák = 1.57E-03). In parallel, in an independent cohort, we compared the blood methylome of converters to AD dementia (n = 54) and non-converters (n = 42), at a preclinical stage. DNA methylation in the same region of the OXT promoter as found in the brain was found to be associated with subsequent conversion to AD dementia in the blood of elderly, non-demented individuals (+ 3.43% 5mC, pŠidák = 7.14E-04).
CONCLUSIONS: The implication of genome-wide significant differential methylation of OXT, encoding oxytocin, in two independent cohorts indicates it is a promising target for future studies on early biomarkers and novel therapeutic strategies in AD.