title: Methylation analysis of DNA repair genes in Alzheimer's disease.
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.
authors.affiliation: 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.
authors.forename: Fabio
authors.initials: F
authors.lastname: Coppedè
authors.affiliation: Department of Translational Research and New Technologies in Medicine and Surgery, Section of Medical Genetics, University of Pisa, Via Roma 55, 56126 Pisa, Italy.
authors.forename: Pierpaola
authors.initials: P
authors.lastname: Tannorella
authors.affiliation: 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.
authors.forename: Andrea
authors.initials: A
authors.lastname: Stoccoro
authors.affiliation: Unit of Neurology, Department of Neuroscience, Pisa University Hospital, Via Roma 67, 56126 Pisa, Italy.
authors.forename: Lucia
authors.initials: L
authors.lastname: Chico
authors.affiliation: 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.
authors.forename: Gabriele
authors.initials: G
authors.lastname: Siciliano
authors.affiliation: 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.
authors.forename: Ubaldo
authors.initials: U
authors.lastname: Bonuccelli
authors.affiliation: 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.
authors.forename: Lucia
authors.initials: L
authors.lastname: Migliore
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000097:blood* / Q000235:genetics*; D019175:DNA Methylation / Q000235:genetics*; D004260:DNA Repair / Q000235:genetics*; D005260:Female; D006801:Humans; D008297:Male; D020411:Oligonucleotide Array Sequence Analysis
keywords: Alzheimer’s disease; DNA methylation; DNA repair; Epigenetics; MGMT; MLH1; MRE11A; OGG1; PARP1 BRCA1