title: The synergistic risk effect of apolipoprotein ε4 and DNA (cytosine-5-)-methyltransferase 3 beta (DNMT3B) haplotype for Alzheimer's disease.
abstract: Alzheimer's disease (AD) is a complex and multifactorial disease with the contribution of several genes and polymorphisms to its development. Among these genes, the APOEε4 is the best known risk factor for AD. Methylation is associated with APOE expression and AD development. Recently, we found an association of the TGG haplotype in the DNMT3B gene, one of the catalyst enzyme for methylation, with AD. Therefore, the objective of the study was to investigate whether APOEε4 and TGG haplotype have an synergistic effect on AD. The sample was composed of 212 Caucasian individuals (108 healthy controls and 104 with AD by NINCDS-ADRDA and DSM-IV-TR criteria) from southern Brazil. The genetic analyses were performed by real time PCR for TaqMan(®) assay. Multivariate logistic regression was performed categorizing groups according to presence of APOEε4 and/or TGG haplotype as an independent variable for outcome AD. The presence of TGG haplotype plus the allele APOEε4 were strongly associated with AD [OR 11.13; 95 % CI (4.25-29.16); P < 0.001]. This association had a higher risk than each risk factor alone. We found a strong association of the interaction of DNMT3B gene with the APOEε4 in this sample of AD patients. The presence of TGG haplotype and APOEε4 significantly increased the risk of developing the disease, showing an synergistic effect.
authors.affiliation: Post Graduate Program in Health Sciences, Universidade Federal de Ciências da Saúde de Porto Alegre, Rua: Taquara 564/306 Bairro Petrópolis, Porto Alegre, RS, 90460210, Brazil.
authors.forename: Cíntia Monique Boschmann Ens
authors.initials: CM
authors.lastname: de Bem
authors.affiliation: Post Graduate Program in Health Sciences, Universidade Federal de Ciências da Saúde de Porto Alegre, Rua: Taquara 564/306 Bairro Petrópolis, Porto Alegre, RS, 90460210, Brazil.
authors.forename: Julio Carlos
authors.initials: JC
authors.lastname: Pezzi
authors.affiliation: Neurology Service, Dementia Clinic, Hospital de Clínicas de Porto Alegre, Porto Alegre, RS, Brazil.
authors.forename: Ericksen Mielle
authors.initials: EM
authors.lastname: Borba
authors.affiliation: Neurology Service, Dementia Clinic, Hospital de Clínicas de Porto Alegre, Porto Alegre, RS, Brazil.
authors.forename: Marcia Lorena Fagundes
authors.initials: ML
authors.lastname: Chaves
authors.affiliation: UniRitter Laureate International Universities, Porto Alegre, RS, Brazil.
authors.forename: Fabiana Michelsen
authors.initials: FM
authors.lastname: de Andrade
authors.affiliation: Post Graduate Program in Health Sciences, Universidade Federal de Ciências da Saúde de Porto Alegre, Rua: Taquara 564/306 Bairro Petrópolis, Porto Alegre, RS, 90460210, Brazil.
authors.forename: Marilu
authors.initials: M
authors.lastname: Fiegenbaum
authors.affiliation: Post Graduate Program in Health Sciences, Universidade Federal de Ciências da Saúde de Porto Alegre, Rua: Taquara 564/306 Bairro Petrópolis, Porto Alegre, RS, 90460210, Brazil. anacamoz@gmail.com.
authors.forename: Analuiza
authors.initials: A
authors.lastname: Camozzato
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000235:genetics*; D053327:Apolipoprotein E4 / Q000235:genetics*; D016022:Case-Control Studies; D004248:DNA (Cytosine-5-)-Methyltransferases / Q000235:genetics*; D004843:Epistasis, Genetic; D005260:Female; D005787:Gene Frequency; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D006239:Haplotypes; D006801:Humans; D008297:Male; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors; D000097584:DNA Methyltransferase 3B
chemical_list: D053327:Apolipoprotein E4; D004248:DNA (Cytosine-5-)-Methyltransferases; D000097584:DNA Methyltransferase 3B
keywords: APOEε4; Alzheimer’s disease; DNMT3B; Epigenetics