Genetic variation in the G720/G30 gene locus (DAOA) influences the occurrence of psychotic symptoms in patients with Alzheimer's disease.
The occurrence of neuropsychiatric symptoms in patients with Alzheimer's disease hampers the clinical management and exacerbates the burden for caregivers. To what extent psychotic symptoms are genetically determined and which are the genes involved has to be established. We tested the hypothesis that the occurrence of delusions and hallucinations in AD is associated with variations in the G72/DAOA gene, which is supposed to play a key role in the glutamate pathway regulated through the NMDA receptors. A panel of single nucleotide polymorphisms were genotyped in a cohort of 185 Alzheimer's disease patients. The analysis demonstrated a nominally significant association (p< 0.05) with one single nucleotide polymorphism (rs2153674). In addition, multivariate regression showed that the rs2153674 genotype accounts for up to 15% of the variance in delusions severity, as assessed by using the Neuropsychiatric Inventory. If the results from the present study will be replicated, the glutamate hypothesis could be invoked to explain the occurrence of psychosis in neurodegenerative disorders.
Di Maria
Emilio
E
Department of Neuroscience, Ophthalmology and Genetics, University of Genova, Genova, Italy. emilio.dimaria@unige.it
Bonvicini
Cristian
C
Bonomini
Cristina
C
Alberici
Antonella
A
Zanetti
Orazio
O
Gennarelli
Massimo
M
D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000150:complications / Q000235:genetics*; D002352:Carrier Proteins / Q000235:genetics*; D002874:Chromosome Mapping; D015331:Cohort Studies; D003702:Delusions / Q000235:genetics / Q000523:psychology; D005260:Female; D005819:Genetic Markers; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005838:Genotype; D006212:Hallucinations / Q000235:genetics / Q000523:psychology; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D008297:Male; D015999:Multivariate Analysis; D009483:Neuropsychological Tests; D020641:Polymorphism, Single Nucleotide; D011618:Psychotic Disorders / Q000209:etiology / Q000235:genetics*
D002352:Carrier Proteins; C475071:DAOA protein, human; D005819:Genetic Markers; D047908:Intracellular Signaling Peptides and Proteins