The synergistic risk effect of apolipoprotein ε4 and DNA (cytosine-5-)-methyltransferase 3 beta (DNMT3B) haplotype for Alzheimer’s disease

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 APOE ε4 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