Alzheimer's Disease and Neurotransmission Gene Variants: Focus on Their Effects on Psychiatric Comorbidities and Inflammatory Parameters.
Aged
Aged, 80 and over
Alzheimer Disease
/ epidemiology
Case-Control Studies
Catechol O-Methyltransferase
/ genetics
Comorbidity
Female
Genetic Predisposition to Disease
/ genetics
Greece
/ epidemiology
Humans
Inflammation
/ epidemiology
Italy
/ epidemiology
Male
Mental Disorders
/ epidemiology
Polymorphism, Single Nucleotide
/ genetics
Sirtuin 1
/ genetics
Synaptic Transmission
/ genetics
Alzheimer’s disease
COMT
Depression
Genetics
Neurotransmission
Oxidative stress
Psychosis
SIRT1
Journal
Neuropsychobiology
ISSN: 1423-0224
Titre abrégé: Neuropsychobiology
Pays: Switzerland
ID NLM: 7512895
Informations de publication
Date de publication:
2019
2019
Historique:
received:
24
04
2018
accepted:
19
01
2019
pubmed:
17
5
2019
medline:
21
12
2019
entrez:
17
5
2019
Statut:
ppublish
Résumé
Alzheimer's disease (AD) is a neurodegenerative disorder accounting for 60-70% of dementia cases. Genetic origin accounts for 49-79% of disease risk. This paper aims to investigate the association of 17 polymorphisms within 7 genes involved in neurotransmission (COMT, HTR2A, PPP3CC, RORA, SIGMAR1, SIRT1, and SORBS3) and AD. A Greek and an Italian sample were investigated, for a total of 156 AD subjects and 301 healthy controls. Exploratory analyses on psychosis and depression comorbidities were performed, as well as on other available clinical and serological parameters. AD was associated with rs4680 within the COMT gene in the total sample. Trends of association were found in the 2 subsamples. Some nominal associations were found for the depressive phenotype. rs10997871 and rs10997875 within SIRT1 were nominally associated with depression in the total sample and in the Greek subsample. rs174696 within COMT was associated with depression comorbidity in the Italian subsample. Our data support the role of COMT, and particularly of rs4680, in the pathogenesis of AD. Furthermore, the SIRT1 gene seems to modulate depressive symptomatology in the AD population.
Sections du résumé
BACKGROUND
BACKGROUND
Alzheimer's disease (AD) is a neurodegenerative disorder accounting for 60-70% of dementia cases. Genetic origin accounts for 49-79% of disease risk. This paper aims to investigate the association of 17 polymorphisms within 7 genes involved in neurotransmission (COMT, HTR2A, PPP3CC, RORA, SIGMAR1, SIRT1, and SORBS3) and AD.
METHODS
METHODS
A Greek and an Italian sample were investigated, for a total of 156 AD subjects and 301 healthy controls. Exploratory analyses on psychosis and depression comorbidities were performed, as well as on other available clinical and serological parameters.
RESULTS
RESULTS
AD was associated with rs4680 within the COMT gene in the total sample. Trends of association were found in the 2 subsamples. Some nominal associations were found for the depressive phenotype. rs10997871 and rs10997875 within SIRT1 were nominally associated with depression in the total sample and in the Greek subsample. rs174696 within COMT was associated with depression comorbidity in the Italian subsample.
DISCUSSION
CONCLUSIONS
Our data support the role of COMT, and particularly of rs4680, in the pathogenesis of AD. Furthermore, the SIRT1 gene seems to modulate depressive symptomatology in the AD population.
Identifiants
pubmed: 31096213
pii: 000497164
doi: 10.1159/000497164
doi:
Substances chimiques
Catechol O-Methyltransferase
EC 2.1.1.6
SIRT1 protein, human
EC 3.5.1.-
Sirtuin 1
EC 3.5.1.-
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
79-85Informations de copyright
© 2019 S. Karger AG, Basel.