Please use this identifier to cite or link to this item: http://hdl.handle.net/2445/126617
Title: Genetic Cross-Interaction between APOE and PRNP in Sporadic Alzheimer's and Creutzfeldt-Jakob Diseases
Author: Calero, Olga
Bullido, María J.
Clarimon, Jordi
Frank García, Ana
Martínez Martín, Pablo
Lleo, Alberto
Rey, María Jesús
Rábano, Alberto
Blesa, Rafael
Gómez Isla, Teresa
Valdivieso, Fernando
Pedro Cuesta, Jesús de
Ferrer, Isidro (Ferrer Abizanda)
Calero, Miguel
Keywords: Malaltia d'Alzheimer
Malaltia de Creutzfeldt-Jakob
Alzheimer's disease
Creutzfeldt-Jakob disease
Issue Date: 20-Jul-2011
Publisher: Public Library of Science (PLoS)
Abstract: Alzheimer's disease (AD) and Creutzfeldt-Jakob disease (CJD) represent two distinct clinical entities belonging to a wider group, generically named as conformational disorders that share common pathophysiologic mechanisms. It is well-established that the APOE epsilon 4 allele and homozygosity at polymorphic codon 129 in the PRNP gene are the major genetic risk factors for AD and human prion diseases, respectively. However, the roles of PRNP in AD, and APOE in CJD are controversial. In this work, we investigated for the first time, APOE and PRNP genotypes simultaneously in 474 AD and 175 sporadic CJD (sCJD) patients compared to a common control population of 335 subjects. Differences in genotype distribution between patients and control subjects were studied by logistic regression analysis using age and gender as covariates. The effect size of risk association and synergy factors were calculated using the logistic odds ratio estimates. Our data confirmed that the presence of APOE epsilon 4 allele is associated with a higher risk of developing AD, while homozygosity at PRNP gene constitutes a risk for sCJD. Opposite, we found no association for PRNP with AD, nor for APOE with sCJD. Interestingly, when AD and sCJD patients were stratified according to their respective main risk genes (APOE for AD, and PRNP for sCJD), we found statistically significant associations for the other gene in those strata at higher previous risk. Synergy factor analysis showed a synergistic age-dependent interaction between APOE and PRNP in both AD (SF = 3.59, p = 0.027), and sCJD (SF = 7.26, p = 0.005). We propose that this statistical epistasis can partially explain divergent data from different association studies. Moreover, these results suggest that the genetic interaction between APOE and PRNP may have a biological correlate that is indicative of shared neurodegenerative pathways involved in AD and sCJD.
Note: Reproducció del document publicat a: https://doi.org/10.1371/journal.pone.0022090
It is part of: PLoS One, 2011, vol. 6, num. 7, p. e22090
URI: http://hdl.handle.net/2445/126617
Related resource: https://doi.org/10.1371/journal.pone.0022090
Appears in Collections:Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL))
Articles publicats en revistes (Patologia i Terapèutica Experimental)

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