Affordable Access

Access to the full text

DNA methylation of TOMM40-APOE-APOC2 in Alzheimer’s disease

Authors
  • Shao, Yvonne1
  • Shaw, McKenzie1
  • Todd, Kaitlin1
  • Khrestian, Maria1
  • D’Aleo, Giana1
  • Barnard, P. John2
  • Zahratka, Jeff1
  • Pillai, Jagan3
  • Yu, Chang-En4
  • Keene, C. Dirk4
  • Leverenz, James B.3
  • Bekris, Lynn M.1
  • 1 Cleveland Clinic, Lerner Research Institute, Genomic Medicine, Cleveland, OH, USA , Cleveland (United States)
  • 2 Cleveland Clinic, Quantitative Health Sciences, Cleveland, OH, USA , Cleveland (United States)
  • 3 Cleveland Clinic, Lou Ruvo Center for Brain Health, Cleveland, OH, USA , Cleveland (United States)
  • 4 Department of Pathology, University of Washington School of Medicine, Seattle, WA, USA , Seattle (United States)
Type
Published Article
Journal
Journal of Human Genetics
Publisher
Springer Nature
Publication Date
Jan 25, 2018
Volume
63
Issue
4
Pages
459–471
Identifiers
DOI: 10.1038/s10038-017-0393-8
Source
Springer Nature
License
Yellow

Abstract

The apolipoprotein E (APOE) ε4 allele is the major genetic risk factor for Alzheimer’s disease (AD). Multiple regulatory elements, spanning the extended TOMM40-APOE-APOC2 region, regulate gene expression at this locus. Regulatory element DNA methylation changes occur under different environmental conditions, such as disease. Our group and others have described an APOE CpG island as hypomethylated in AD, compared to cognitively normal controls. However, little is known about methylation of the larger TOMM40-APOE-APOC2 region. The hypothesis of this investigation was that regulatory element methylation levels of the larger TOMM40-APOE-APOC2 region are associated with AD. The aim was to determine whether DNA methylation of the TOMM40-APOE-APOC2 region differs in AD compared to cognitively normal controls in post-mortem brain and peripheral blood. DNA was extracted from human brain (n = 12) and peripheral blood (n = 67). A methylation array was used for this analysis. Percent methylation within the TOMM40-APOE-APOC2 region was evaluated for differences according to tissue type, disease state, AD-related biomarkers, and gene expression. Results from this exploratory analysis suggest that regulatory element methylation levels within the larger TOMM40-APOE-APOC2 gene region correlate with AD-related biomarkers and TOMM40 or APOE gene expression in AD.

Report this publication

Statistics

Seen <100 times