title: DNA methyltransferase haplotype is associated with Alzheimer's disease.
abstract: Epigenetic mechanisms have been implicated in syndromes associated with neuropsychiatric disorders, but little is known about the role of epigenetics in Alzheimer's disease (AD). DNA methylation, one of the main epigenetic mechanisms, is a complex process carried out by specific enzymes, such as DNMT1 and DNMT3B. This study aimed to investigate the association between DNMT1 and DNMT3B polymorphisms and AD. Two hundred and ten elderly subjects (108 healthy controls and 102 with AD-NINCDS/ARDA, DSM-IV-TR criteria) were assessed. DNA was obtained from whole blood, and genotypes were detected by an allelic discrimination assay using TaqMan(®) MGB probes on a real-time PCR system. The polymorphisms studied were rs2162560, rs759920 (DNMT1) and rs998382, rs2424913, rs2424932 (DNMT3B). For both genes, the polymorphisms were in strong linkage disequilibrium. Carriers of the DNMT3B TGG haplotype were associated with AD (OR=3.03, 95% CI 1.63 to 5.63, P<0.001). No significant difference between AD and the control group were observed for DNMT1 polymorphisms. This study is one of the first describing a significant association between DNMT3B polymorphisms and AD. This enzyme, which is responsible for methylation in a general way, may be involved in AD.
authors.affiliation: Graduate Program in Health Science, Universidade Federal de Ciências da Saúde de Porto Alegre, Porto Alegre, RS, Brazil. Electronic address: julio@pezzi.com.br.
authors.forename: Julio Carlos
authors.initials: JC
authors.lastname: Pezzi
authors.affiliation: Graduate Program in Health Science, Universidade Federal de Ciências da Saúde de Porto Alegre, Porto Alegre, RS, Brazil.
authors.forename: Cintia Monique Boschmann
authors.initials: CM
authors.lastname: Ens
authors.affiliation: Dementia Clinic, Neurology Service, Hospital de Clinicas de Porto Alegre, Porto Alegre, RS, Brazil.
authors.forename: Ericksen Mielle
authors.initials: EM
authors.lastname: Borba
authors.affiliation: Dementia Clinic, Neurology Service, Hospital de Clinicas de Porto Alegre, Porto Alegre, RS, Brazil.
authors.forename: Artur F
authors.initials: AF
authors.lastname: Schumacher-Schuh
authors.affiliation: Graduate Program in Biomedicine, Universidade Feevale, Novo Hamburgo. RS, Brazil.
authors.forename: Fabiana Michelsen
authors.initials: FM
authors.lastname: de Andrade
authors.affiliation: Dementia Clinic, Neurology Service, Hospital de Clinicas de Porto Alegre, Porto Alegre, RS, Brazil.
authors.forename: Marcia Lorena Fagundes
authors.initials: ML
authors.lastname: Chaves
authors.affiliation: Graduate Program in Health Science, Universidade Federal de Ciências da Saúde de Porto Alegre, Porto Alegre, RS, Brazil.
authors.forename: Marilu
authors.initials: M
authors.lastname: Fiegenbaum
authors.affiliation: Graduate Program in Health Science, Universidade Federal de Ciências da Saúde de Porto Alegre, Porto Alegre, RS, Brazil.
authors.forename: Ana Luiza
authors.initials: AL
authors.lastname: Camozzato
mesh_terms: D000368:Aged; D000544:Alzheimer Disease / Q000235:genetics*; D016022:Case-Control Studies; D000076123:DNA (Cytosine-5-)-Methyltransferase 1; D004248:DNA (Cytosine-5-)-Methyltransferases / Q000235:genetics*; D015254:DNA Modification Methylases / Q000235:genetics*; D044127:Epigenesis, Genetic; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D006239:Haplotypes / Q000235:genetics*; D006801:Humans; D007527:Isoenzymes / Q000235:genetics; D008297:Male; D009483:Neuropsychological Tests; D010641:Phenotype; D011110:Polymorphism, Genetic / Q000235:genetics; D000097584:DNA Methyltransferase 3B
chemical_list: D000076123:DNA (Cytosine-5-)-Methyltransferase 1; D004248:DNA (Cytosine-5-)-Methyltransferases; D015254:DNA Modification Methylases; D007527:Isoenzymes; D000097584:DNA Methyltransferase 3B; C000619380:DNMT1 protein, human
keywords: Alzheimer's disease; Epigenomics; Methyltransferases; Single nucleotide polymorphism