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 Ruiz; Joan Xavier Comella

doi:10.3233/JAD-142721

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

Department of Psychiatry

Research output: Contribution to journal › Article › peer-review

4 Scopus citations

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.

Original language	English
Pages (from-to)	621-629
Number of pages	9
Journal	Journal of Alzheimer's Disease
Volume	45
Issue number	2
DOIs	https://doi.org/10.3233/JAD-142721
State	Published - 2015

Keywords

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

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10.3233/JAD-142721

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Moreno-Grau, S., Barneda, B., Carriba, P., Marín, J., Sotolongo-Grau, O., Hernández, I., Rosende-Roca, M., Mauleón, A., Vargas, L., Espinosa, A., Alegret, M., Rodriguez, O., Ortega, G., Fernández, M. V., López-Arrieta, J., Tárraga, L., Boada, M., Antúnez, C., López, J., ... Comella, J. X. (2015). Evaluation of Candidate Genes Related to Neuronal Apoptosis in Late-Onset Alzheimer's Disease. Journal of Alzheimer's Disease, 45(2), 621-629. https://doi.org/10.3233/JAD-142721

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

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.",

keywords = "Alzheimer's disease, FASLG, TNF, apoptosis, death receptors, genetics, genome-wide association study, meta-analysis",

author = "Sonia Moreno-Grau and Bruna Barneda and Paulina Carriba and Juan Mar{\'i}n and Oscar Sotolongo-Grau and Isabel Hern{\'a}ndez and Mait{\'e}e Rosende-Roca and Ana Maule{\'o}n and Liliana Vargas and Ana Espinosa and Montserrat Alegret and Octavio Rodriguez and Gemma Ortega and Fern{\'a}ndez, {Maria Victoria} and Jes{\'u}s L{\'o}pez-Arrieta and Llu{\'i}s T{\'a}rraga and Merc{\`e} Boada and Carmen Ant{\'u}nez and Joaquin L{\'o}pez and Agust{\'i}n Ruiz and Comella, {Joan Xavier}",

year = "2015",

doi = "10.3233/JAD-142721",

language = "English",

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Moreno-Grau, S, Barneda, B, Carriba, P, Marín, J, Sotolongo-Grau, O, Hernández, I, Rosende-Roca, M, Mauleón, A, Vargas, L, Espinosa, A, Alegret, M, Rodriguez, O, Ortega, G, Fernández, MV, López-Arrieta, J, Tárraga, L, Boada, M, Antúnez, C, López, J, Ruiz, A & Comella, JX 2015, 'Evaluation of Candidate Genes Related to Neuronal Apoptosis in Late-Onset Alzheimer's Disease', Journal of Alzheimer's Disease, vol. 45, no. 2, pp. 621-629. https://doi.org/10.3233/JAD-142721

TY - JOUR

T1 - Evaluation of Candidate Genes Related to Neuronal Apoptosis in Late-Onset Alzheimer's Disease

AU - Moreno-Grau, Sonia

AU - Barneda, Bruna

AU - Carriba, Paulina

AU - Marín, Juan

AU - Sotolongo-Grau, Oscar

AU - Hernández, Isabel

AU - Rosende-Roca, Maitée

AU - Mauleón, Ana

AU - Vargas, Liliana

AU - Espinosa, Ana

AU - Alegret, Montserrat

AU - Rodriguez, Octavio

AU - Ortega, Gemma

AU - Fernández, Maria Victoria

AU - López-Arrieta, Jesús

AU - Tárraga, Lluís

AU - Boada, Mercè

AU - Antúnez, Carmen

AU - López, Joaquin

AU - Ruiz, Agustín

AU - Comella, Joan Xavier

PY - 2015

Y1 - 2015

N2 - 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.

AB - 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.

KW - Alzheimer's disease

KW - FASLG

KW - TNF

KW - apoptosis

KW - death receptors

KW - genetics

KW - genome-wide association study

KW - meta-analysis

UR - http://www.scopus.com/inward/record.url?scp=84925344528&partnerID=8YFLogxK

U2 - 10.3233/JAD-142721

DO - 10.3233/JAD-142721

M3 - Article

C2 - 25613099

AN - SCOPUS:84925344528

SN - 1387-2877

VL - 45

SP - 621

EP - 629

JO - Journal of Alzheimer's Disease

JF - Journal of Alzheimer's Disease

IS - 2

ER -

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

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Keywords

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