Evaluation of Candidate Genes Related to Neuronal Apoptosis in Late-Onset Alzheimer’s Disease

J Alzheimers Dis. 2015;45(2):621-9. doi: 10.3233/JAD-142721.

Abstract

The objective of this study was to identify genetic variation in genes encoding death receptors and signals that modulate their activity. After conducting a meta-analysis with five previous genome-wide association studies and aggregated data, the most significant signals, (TNF locus: rs2395488, rs2534672, and rs9267445; and FASLG locus: rs730278), were replicated in 1,046 cases and 372 controls. The rs2395488 and rs2534672 markers showed a modest protective effect (OR = 0.849, p = 0.49780;OR= 0.687, p = 0.11335), in contrast to rs730278 marker (OR = 1.146, p = 0.17212), which did not follow the previous effect direction; in any case it reached the significance level. Final meta-analysis, adding the replication sample, confirmed these observations. We concluded that FASLG marker is not etiologically linked to Alzheimer’s disease. However, single nucleotide polymorphisms around TNF locus require further analyses in order to explain the association between Alzheimer’s disease and human leukocyte antigen.

Publication types

  • Multicenter Study
  • Observational Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Alzheimer Disease / drug therapy
  • Alzheimer Disease / genetics
  • Alzheimer Disease / pathology
  • Analysis of Variance
  • Apolipoproteins E / genetics
  • Apoptosis / drug effects
  • Apoptosis / genetics*
  • Cholinesterase Inhibitors / therapeutic use*
  • Cytochrome P-450 CYP2D6 / genetics
  • Donepezil
  • Fas Ligand Protein / genetics
  • Female
  • Humans
  • Indans / therapeutic use
  • Longitudinal Studies
  • Male
  • Mental Status Schedule
  • Meta-Analysis as Topic
  • Pharmacogenetics*
  • Piperidines / therapeutic use
  • Polymorphism, Genetic / genetics*
  • Predictive Value of Tests
  • Treatment Outcome
  • Tumor Necrosis Factor-alpha / genetics*

Substances

  • Apolipoproteins E
  • Cholinesterase Inhibitors
  • FASLG protein, human
  • Fas Ligand Protein
  • Indans
  • Piperidines
  • TNF protein, human
  • Tumor Necrosis Factor-alpha
  • Donepezil
  • Cytochrome P-450 CYP2D6