Abstract
The vast majority of Alzheimer’s disease (AD) are late-onset forms (LOAD) likely due to the contribution of genetic, environmental, and stochastic factors, superimposed on a physiologically age-related decline of neuronal functions. Increasing evidence indicates epigenetic modifications in LOAD brains, and many of the environmental factors associated with AD risk, such as heavy metals and dietary factors, are able to modify the epigenome. There is also indication that environmentally-induced early life modifications of the genome during embryogenesis and brain development could contribute to the development of the disease later in life. DNA methyltransferase 3b (DNMT3b) is an enzyme involved in de novo methylation of the genome during embryogenesis, expressed in progenitor cells during neurogenesis. In the present study we evaluated two functional DNMT3B promoter polymorphisms, namely -149 C>T (rs2424913) and - 579 G>T (rs1569686), as candidate LOAD risk factors. Our analysis of 376 Italian LOAD patients and 308 matched controls revealed no difference in allele frequencies between the case an the control group (OR = 1.10 (0.88-1.39) for rs2424913, and OR = 1.02 (0.81-1.28) for rs1569686). Also the genotype distributions of both polymorphisms were closely similar between groups, and no significant effect on disease age at onset was observed. Overall, present results do not support a major role for rs2424913 or rs1569686 in LOAD pathogenesis.
Keywords: Alzheimer’s disease, epigenetics, DNA methyltransferases, DNMT3B, polymorphisms, DNA methylation.
Current Alzheimer Research
Title:DNMT3B Promoter Polymorphisms and Risk of Late Onset Alzheimer’s Disease
Volume: 9 Issue: 5
Author(s): Fabio Coppede, Maria Teresa Zitarosa, Francesca Migheli, Annalisa Lo Gerfo, Silvia Bagnoli, Angela Dardano, Benedetta Nacmias, Michelangelo Mancuso, Fabio Monzani, Gabriele Siciliano, Sandro Sorbi and Lucia Migliore
Affiliation:
Keywords: Alzheimer’s disease, epigenetics, DNA methyltransferases, DNMT3B, polymorphisms, DNA methylation.
Abstract: The vast majority of Alzheimer’s disease (AD) are late-onset forms (LOAD) likely due to the contribution of genetic, environmental, and stochastic factors, superimposed on a physiologically age-related decline of neuronal functions. Increasing evidence indicates epigenetic modifications in LOAD brains, and many of the environmental factors associated with AD risk, such as heavy metals and dietary factors, are able to modify the epigenome. There is also indication that environmentally-induced early life modifications of the genome during embryogenesis and brain development could contribute to the development of the disease later in life. DNA methyltransferase 3b (DNMT3b) is an enzyme involved in de novo methylation of the genome during embryogenesis, expressed in progenitor cells during neurogenesis. In the present study we evaluated two functional DNMT3B promoter polymorphisms, namely -149 C>T (rs2424913) and - 579 G>T (rs1569686), as candidate LOAD risk factors. Our analysis of 376 Italian LOAD patients and 308 matched controls revealed no difference in allele frequencies between the case an the control group (OR = 1.10 (0.88-1.39) for rs2424913, and OR = 1.02 (0.81-1.28) for rs1569686). Also the genotype distributions of both polymorphisms were closely similar between groups, and no significant effect on disease age at onset was observed. Overall, present results do not support a major role for rs2424913 or rs1569686 in LOAD pathogenesis.
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Coppede Fabio, Teresa Zitarosa Maria, Migheli Francesca, Lo Gerfo Annalisa, Bagnoli Silvia, Dardano Angela, Nacmias Benedetta, Mancuso Michelangelo, Monzani Fabio, Siciliano Gabriele, Sorbi Sandro and Migliore Lucia, DNMT3B Promoter Polymorphisms and Risk of Late Onset Alzheimer’s Disease, Current Alzheimer Research 2012; 9 (5) . https://dx.doi.org/10.2174/156720512800618062
DOI https://dx.doi.org/10.2174/156720512800618062 |
Print ISSN 1567-2050 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5828 |
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