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Mech Ageing Dev. 2017 Jan;161(Pt A):105-111. doi: 10.1016/j.mad.2016.04.003. Epub 2016 Apr 11.

Methylation analysis of DNA repair genes in Alzheimer's disease.

Author information

1
Department of Translational Research and New Technologies in Medicine and Surgery, Section of Medical Genetics, University of Pisa, Via Roma 55, 56126 Pisa, Italy. Electronic address: fabio.coppede@med.unipi.it.
2
Department of Translational Research and New Technologies in Medicine and Surgery, Section of Medical Genetics, University of Pisa, Via Roma 55, 56126 Pisa, Italy.
3
Department of Translational Research and New Technologies in Medicine and Surgery, Section of Medical Genetics, University of Pisa, Via Roma 55, 56126 Pisa, Italy; Doctoral School in Genetics Oncology and Clinical Medicine, University of Siena, Siena, Italy.
4
Unit of Neurology, Department of Neuroscience, Pisa University Hospital, Via Roma 67, 56126 Pisa, Italy.
5
Unit of Neurology, Department of Neuroscience, Pisa University Hospital, Via Roma 67, 56126 Pisa, Italy; Department of Clinical and Experimental Medicine, University of Pisa, Neurological Clinic, Via Roma 67, 56126 Pisa, Italy.
6
Department of Translational Research and New Technologies in Medicine and Surgery, Section of Medical Genetics, University of Pisa, Via Roma 55, 56126 Pisa, Italy. Electronic address: lucia.migliore@med.unipi.it.

Abstract

There is substantial evidence of impaired DNA repair activities in Alzheimer's disease (AD) neurons and peripheral tissues, inducing some investigators to speculate that this could partially result from promoter hypermethylation of DNA repair genes, resulting in gene silencing in those tissues. In the present study a screening cohort composed by late-onset AD (LOAD) patients and healthy matched controls was evaluated with a commercially available DNA methylation array for the assessment of the methylation levels of a panel of 22 genes involved in major DNA repair pathways in blood DNA. We then applied a cost-effective PCR based methylation-sensitive high-resolution melting (MS-HRM) technique, in order to evaluate the promoter methylation levels of the following DNA repair genes: OGG1, PARP1, MRE11A, BRCA1, MLH1, and MGMT. The analysis was performed in blood DNA from 56 LOAD patients and 55 matched controls, including the samples previously assessed with the DNA methylation array as validating samples. Both approaches revealed that all the investigated genes were largely hypomethylated in LOAD and control blood DNA, and no difference between groups was observed. Collectively, present data do not support an increased promoter methylation of some of the major DNA repair genes in blood DNA of AD patients.

KEYWORDS:

Alzheimer’s disease; DNA methylation; DNA repair; Epigenetics; MGMT; MLH1; MRE11A; OGG1; PARP1 BRCA1

PMID:
27080585
DOI:
10.1016/j.mad.2016.04.003
[Indexed for MEDLINE]

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