title: Association study between the DNMT3A -448A>G polymorphism and risk of Alzheimer's disease in Caucasians of Italian origin.
abstract: Increasing evidence points to an epigenetic contribution in Alzheimer's disease (AD) pathogenesis. In this regard, variants and polymorphisms of DNA methyltransferase genes (DNMTs) are being investigated for their contribution to cognitive decline and dementia, but results are still scarce or controversial. In the present study we genotyped 710 Caucasian subjects of Italian descent, including 320 late-onset AD (LOAD) patients, 70 individuals with amnestic Mild Cognitive Impairment (MCI), and 320 matched healthy controls, for the presence of a functional DNMT3A -448A>G (rs1550117) polymorphism, searching for association with disease risk. In addition, we searched for correlation between the studied polymorphism and circulating levels of folate, homocysteine (hcy) and vitamin B12, all involved in DNA methylation reactions and available from 189 LOAD patients and 186 matched controls. Both allele and genotype frequencies of rs1550117 were closely similar between MCI, LOAD and control subjects, and no association with dementia or pre-dementia conditions was observed. Plasma hcy levels were significantly higher (p = 0.04) and serum folate levels significantly lower (p = 0.01) in LOAD than in controls, but no difference in circulating folate, hcy or vitamin B12 levels was seen between carriers and non-carriers of the minor DNMT3A -448A allele. Collectively, present results confirmed previous associations of increased hcy and decreased folate with LOAD risk, but do not support an association between the DNMT3A -448A>G polymorphism and AD in our population.
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 PisaVia Roma 55, 56126 Pisa, Italy; Doctoral School in Genetics Oncology and Clinical Medicine, University of SienaSiena, 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: Gloria
authors.initials: G
authors.lastname: Tognoni
authors.affiliation: Unit of Neurology, Department of Neuroscience, Pisa University HospitalVia Roma 67, 56126 Pisa, Italy; Department of Clinical and Experimental Medicine, University of Pisa, Neurological ClinicVia 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 PisaVia Roma 55, 56126 Pisa, Italy; Interdepartmental Research Center Nutrafood "Nutraceuticals and Food for Health", University of PisaVia del Borghetto 80, 56124 Pisa, Italy.
authors.forename: Lucia
authors.initials: L
authors.lastname: Migliore
authors.affiliation: Department of Translational Research and New Technologies in Medicine and Surgery, Section of Medical Genetics, University of PisaVia Roma 55, 56126 Pisa, Italy; Interdepartmental Research Center Nutrafood "Nutraceuticals and Food for Health", University of PisaVia del Borghetto 80, 56124 Pisa, Italy.
authors.forename: Fabio
authors.initials: F
authors.lastname: Coppedè
keywords: Alzheimer’s disease; DNMT3A -448A>G polymorphism; Mild Cognitive Impairment; epigenetics; folate; homocysteine; rs1550117