The Synergistic Risk Effect of Apolipoprotein ε4 and DNA (cytosine-5-)-methyltransferase 3 Beta (DNMT3B) Haplotype for Alzheimer's Disease

Overview

Journal Mol Biol Rep

Specialty Molecular Biology

Date 2016 May 19

PMID 27188425

Citations 5

Authors

Cintia Monique Boschmann Ens de Bem

Julio Carlos Pezzi

Ericksen Mielle Borba

Marcia Lorena Fagundes Chaves

Fabiana Michelsen de Andrade

Marilu Fiegenbaum

Analuiza Camozzato

Affiliations

Soon will be listed here.

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.

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