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

Sonia Moreno-Grau, Bruna Barneda, Paulina Carriba, Juan Marín, Oscar Sotolongo-Grau, Isabel Hernández, Maitée Rosende-Roca, Ana Mauleón, Liliana Vargas, Ana Espinosa, Montserrat Alegret, Octavio Rodriguez, Gemma Ortega, Maria Victoria Fernández, Jesús López-Arrieta, Lluís Tárraga, Mercè Boada, Carmen Antúnez, Joaquin López, Agustín RuizJoan Xavier Comella

Research output: Contribution to journalArticlepeer-review

4 Scopus citations


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.

Original languageEnglish
Pages (from-to)621-629
Number of pages9
JournalJournal of Alzheimer's Disease
Issue number2
StatePublished - 2015


  • Alzheimer's disease
  • TNF
  • apoptosis
  • death receptors
  • genetics
  • genome-wide association study
  • meta-analysis


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