title: DNMT3B promoter polymorphisms and risk of late onset Alzheimer's disease.
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.
authors.affiliation: Faculty of Medicine, University of Pisa, Italy. f.coppede@geog.unipi.it
authors.forename: Fabio
authors.initials: F
authors.lastname: Coppedè
authors.forename: Maria Teresa
authors.initials: MT
authors.lastname: Zitarosa
authors.forename: Francesca
authors.initials: F
authors.lastname: Migheli
authors.forename: Annalisa
authors.initials: A
authors.lastname: Lo Gerfo
authors.forename: Silvia
authors.initials: S
authors.lastname: Bagnoli
authors.forename: Angela
authors.initials: A
authors.lastname: Dardano
authors.forename: Benedetta
authors.initials: B
authors.lastname: Nacmias
authors.forename: Michelangelo
authors.initials: M
authors.lastname: Mancuso
authors.forename: Fabio
authors.initials: F
authors.lastname: Monzani
authors.forename: Gabriele
authors.initials: G
authors.lastname: Siciliano
authors.forename: Sandro
authors.initials: S
authors.lastname: Sorbi
authors.forename: Lucia
authors.initials: L
authors.lastname: Migliore
mesh_terms: D017668:Age of Onset; D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000235:genetics*; D000704:Analysis of Variance; D016022:Case-Control Studies; D004248:DNA (Cytosine-5-)-Methyltransferases / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D059647:Gene-Environment Interaction; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D016555:Matched-Pair Analysis; D016017:Odds Ratio; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic / Q000235:genetics*; D012016:Reference Values; D012307:Risk Factors; D000097584:DNA Methyltransferase 3B
chemical_list: D004248:DNA (Cytosine-5-)-Methyltransferases; D000097584:DNA Methyltransferase 3B