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.
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