The GAB2 and BDNF polymorphisms and the risk for late-onset Alzheimer's disease in an elderly Brazilian sample

Int Psychogeriatr. 2015 Oct;27(10):1687-92. doi: 10.1017/S1041610215000514. Epub 2015 Apr 8.

Abstract

Background: Evidences suggest that GAB2 and BDNF genes may be associated with Alzheimer's disease (AD). We aimed to investigate the GAB2 rs2373115 and BDNF rs6265 polymorphisms and the risk of AD in a Brazilian sample.

Methods: 269 AD patients and 114 controls were genotyped with Real-time PCR. Multifactor dimensionality reduction (MDR) was employed to explore the effects of gene-gene interactions.

Results: GAB2 and BDNF were not associated with AD in our sample. Nevertheless BDNF Val allele (rs6265) presented a synergic association with the APOE ε4 allele. A multiple logistic regression demonstrated that the APOE ε4 allele and years of education were the best predictors for AD. In ε4 non-carriers sex, education and hypertension were independently correlated with AD, while in ε4 carriers we did not observe any association. The findings were further confirmed by bootstrapping method.

Conclusions: Our data suggest that the interaction of BDNF and APOE has significant effect on AD. Moreover in absence of ε4, female sex, low level of education and hypertension are independently associated with AD. Interventions aimed to prevent AD should focus on these factors and also taking into account the APOE alleles.

Keywords: APOE; Alzheimer’s disease; BDNF; GAB2; risk factors.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Alleles
  • Alzheimer Disease / genetics*
  • Apolipoprotein E4 / genetics*
  • Brain-Derived Neurotrophic Factor / genetics*
  • Brazil
  • Case-Control Studies
  • Female
  • Genetic Predisposition to Disease
  • Humans
  • Logistic Models
  • Male
  • Middle Aged
  • Polymorphism, Genetic
  • Risk Factors

Substances

  • Apolipoprotein E4
  • Brain-Derived Neurotrophic Factor