title: Is HCRTR2 a genetic risk factor for Alzheimer's disease?
abstract: OBJECTIVE
  Alzheimer's disease (AD) is one of the main types of dementia affecting about 50-55% of all demented patients. Sleep disturbances in AD patients are associated with the severity of dementia and are often the primary reason for institutionalization. These sleep problems partly resemble the core symptoms of narcolepsy, a sleep disorder caused by a general loss of the neurotransmitter hypocretin. The aim of our study was to investigate whether genetic variants in the hypocretin (HCRT) and in the hypocretin receptors 1 and 2 (HCRTR1, HCRTR2) genes could modify the occurrence and the clinical features of AD and to examine if these possible variants influence the role of the protein in sleep regulation.
  
  
  METHODS
  Using a case-control strategy, we genotyped 388 AD patients and 272 controls for 10 SNPs in the HCRT, HCRTR1 and HCRTR2 genes. In order to evaluate which residues belong to the HCRTR2 binding site, we built a molecular model.
  
  
  RESULTS
  The genotypic and allelic frequencies of the rs2653349 polymorphism were different (χ(2) = 5.77, p = 0.016; χ(2) = 6.728, p = 0.035) between AD patients and controls. The carriage of the G allele was associated with an increased AD risk (OR 2.53; 95% CI 1.10-5.80). No significant differences were found in the distribution of either genotypic or allelic frequencies between cases and controls in the HCRTR1 polymorphisms rs2271933, rs10914456 and rs4949449 and in the HCRTR2 polymorphism rs3122156.
  
  
  CONCLUSIONS
  Our data support the hypothesis that the HCRTR2 gene is likely to be a risk factor for AD. The increased risk inferred is quite small, but in the context of a multi-factorial disease, the presence of this polymorphism may significantly contribute to influencing the susceptibility for AD by interacting with other unknown genetic or environmental factors in sleep regulation.
authors: Neurology II, Department of Neuroscience, University of Turin, Turin, Italy.
authors: Salvatore
authors: S
authors: Gallone
authors: Silvia
authors: S
authors: Boschi
authors: Elisa
authors: E
authors: Rubino
authors: Paola
authors: P
authors: De Martino
authors: Elio
authors: E
authors: Scarpini
authors: Daniela
authors: D
authors: Galimberti
authors: Chiara
authors: C
authors: Fenoglio
authors: Pier Luigi
authors: PL
authors: Acutis
authors: Maria Grazia
authors: MG
authors: Maniaci
authors: Lorenzo
authors: L
authors: Pinessi
authors: Innocenzo
authors: I
authors: Rainero
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D000544:Alzheimer Disease / Q000235:genetics*; D016022:Case-Control Studies; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics*; D008297:Male; D009479:Neuropeptides / Q000235:genetics*; D064446:Orexin Receptors / Q000235:genetics*; D000068797:Orexins; D020641:Polymorphism, Single Nucleotide
chemical_list: C578630:HCRTR1 protein, human; C578626:HCRTR2 protein, human; D047908:Intracellular Signaling Peptides and Proteins; D009479:Neuropeptides; D064446:Orexin Receptors; D000068797:Orexins