The Genetic Variability of UCP4 Affects the Individual Susceptibility to Late-Onset Alzheimer's Disease and Modifies the Disease's Risk in APOE-É4 Carriers.
J Alzheimers Dis
; 51(4): 1265-74, 2016.
Article
em En
| MEDLINE
| ID: mdl-26923023
ABSTRACT
Uncoupling proteins (UCPs) are a group of five mitochondrial inner membrane transporters with a tissue specific expression that uncouple biofuel oxidation from ATP synthesis and function as regulators of energy homeostasis and antioxidants. Previous data suggested that neuronal UCPs (UCP2, UCP4, and UCP5) can directly influence synaptic plasticity, neurotransmission, and neurodegenerative processes, and have a crucial role in the function and protection of the central nervous system. In fact, it has been observed that the expression of neuronal UCPs significantly decreases in Alzheimer's disease (AD) patients. Here we analyzed the variability of UCP2, -3, -4, and 5 genes in sporadic and familial cases (nâ=â465) of late-onset AD (LOAD) with respect to healthy controls (nâ=â442). We showed that a genetic variant in the human UCP4, rs9472817, not only significantly affects the individual susceptibility to LOAD, but also modulates the effect of APOE-É4 on AD risk. In fact, rs9472817-C allele was significantly more frequent in both groups of patients with respect to the control group (pâ=â6.934*10-4 for familial and pâ=â1.033*10-3 for sporadic cases). In addition, gene-gene interaction analysis revealed that the effect of APOE-É4 allele on LOAD risk was doubled in homozygote CC subjects; conversely, the risk conferred by the APOE-É4 allele was annulled in subjects with two copies of the G allele. Our findings are further evidence that the efficiency in mitochondrial energy metabolism and oxidative stress are important factors in AD pathogenesis.
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Texto completo:
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Polimorfismo de Nucleotídeo Único
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Apolipoproteína E4
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Doença de Alzheimer
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Proteínas de Desacoplamento Mitocondrial
Tipo de estudo:
Etiology_studies
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Prognostic_studies
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Risk_factors_studies
Limite:
Aged
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Aged80
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Female
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Humans
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Male
Idioma:
En
Ano de publicação:
2016
Tipo de documento:
Article