DNMT3A moderates cognitive decline in subjects with mild cognitive impairment: replicated evidence from two mild cognitive impairment cohorts

Leonidas Chouliaras; Gunter Kenis; Pieter Jelle Visser; Philip Scheltens; Magda Tsolaki; Roy W Jones; Patrick G Kehoe; Caroline Graff; Nicola G Girtler; Åsa K Wallin; Marcel Olde Rikkert; Luiza Spiru; Lyzel S Elias-Sonnenschein; Inez H G B Ramakers; Ehsan Pishva; Jim van Os; Harry W M Steinbusch; Frans R J Verhey; Daniel L A van den Hove; Bart P F Rutten

doi:10.2217/epi.15.22

DNMT3A moderates cognitive decline in subjects with mild cognitive impairment: replicated evidence from two mild cognitive impairment cohorts

Epigenomics. 2015;7(4):533-7. doi: 10.2217/epi.15.22.

Authors

Leonidas Chouliaras¹, Gunter Kenis¹, Pieter Jelle Visser^{1

2}, Philip Scheltens², Magda Tsolaki³, Roy W Jones⁴, Patrick G Kehoe⁵, Caroline Graff⁶, Nicola G Girtler⁷, Åsa K Wallin⁸, Marcel Olde Rikkert⁹, Luiza Spiru¹⁰, Lyzel S Elias-Sonnenschein¹, Inez H G B Ramakers¹, Ehsan Pishva¹, Jim van Os¹, Harry W M Steinbusch¹, Frans R J Verhey¹, Daniel L A van den Hove¹, Bart P F Rutten^{1

11}

Affiliations

¹ Department of Psychiatry & Neuropsychology, School for Mental Health & Neuroscience, European Graduate School of Neuroscience (EURON), Maastricht University Medical Centre, Maastricht, The Netherlands.
² Department of Neurology, Alzheimer Center, VU University Medical Center, Amsterdam, The Netherlands.
³ Aristotle University of Thessaloniki, Memory & Dementia Center, 3rd Department of Neurology, G Papanicolaou General Hospital, Thessaloniki, Greece.
⁴ The Research Institute for the Care of Older People (RICE), Bath, UK.
⁵ School of Clinical Sciences, Dementia Research Group, University of Bristol Frenchay Hospital, Bristol, UK.
⁶ Department of Neurobiology, Care Sciences & Society, Karolinska Institutet, Huddinge, Sweden.
⁷ Clinical Neurology, Department of Neuroscience (DINOGMI), University of Genoa, Italy.
⁸ Clinical Memory Research Unit, Department of Clinical Sciences Malmö, Lund University, Sweden.
⁹ Radboud Alzheimer Center, Department of Geriatrics, Donders Institute for Cognitive Neurosciences, Radboud University Medical Center, Nijmegen, The Netherlands.
¹⁰ "Carol Davila" University of Medicine & Pharmacy, Bucharest, Romania.
¹¹ Department of Psychiatry & Psychology, Faculty of Health, Medicine & Life Sciences, School for Mental Health & Neuroscience (MHeNS), European Graduate School of Neuroscience (EURON), Maastricht University Medical Centre, Universiteitssingel 50, 6229 ER, PO Box 616 6200 MD, Maastricht, The Netherlands.

PMID: 26111027
DOI: 10.2217/epi.15.22

Abstract

Epigenetic dysregulation has been associated with cognitive decline and Alzheimer's disease. The present study investigated associations between common SNPs in genes regulating DNA methylation and age-related changes in cognitive decline in two independent prospective cohorts of patients suffering from mild cognitive impairment. An association between the rs1187120 SNP in DNMT3A and annual decline in cognitive functioning was discovered and replicated, suggesting that DNMT3A moderates cognitive decline in subjects with mild cognitive impairment.

Keywords: DNA methylation; DNMT3A; MCI; SNP; aging; epigenetics; mild cognitive impairment.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Aged
Case-Control Studies
Cognition
Cognitive Dysfunction / genetics*
DNA (Cytosine-5-)-Methyltransferases / genetics*
DNA Methyltransferase 3A
Female
Humans
Male
Middle Aged
Polymorphism, Single Nucleotide*

Substances

DNMT3A protein, human
DNA (Cytosine-5-)-Methyltransferases
DNA Methyltransferase 3A