Association between major mood disorders and the hypocretin receptor 1 gene.
BACKGROUND
Recent studies suggested a role for hypocretins in the neurobiology of Major Mood Disorders (MMD). The purpose of this study was to investigate hypocretin involvement in MMD evaluating whether particular alleles or genotypes of the hypocretin pathway genes (HCRT, HCRTR1 and HCRTR2) would modify the occurrence and clinical features of the disease.


METHODS
We selected for the study 229 MMD patients and 259 healthy age-, sex- and ethnicity-matched controls. Cases and controls were genotyped for several single-nucleotide polymorphisms (SNPs) of the HCRT, HCRTR1, and HCRTR2 genes.


RESULTS
We found that allelic and genotypic frequencies of the rs2271933 G>A polymorphism (Ile408Val) in the HCRTR1 gene were significantly different between cases and controls (p=0.003 and p=0.0004, respectively). The carriage of the A allele was associated with a significantly increased disease risk (OR:1.60, 95% C.I. 1.22-2.10). In addition, we found a significant association between HCRTR1 haplotypes and the disease (permutation p<0.0001). In the analysis of subgroups we confirmed the association only in patients with unipolar depression.


CONCLUSIONS
Our sample was relatively small and included only cases and controls recruited from Northern Italy. Analysis of the disease subgroups warrants reexamination with more subjects. Finally, the effects of the rs2271933 G>A polymorphism on the hypocretin-1 receptor function are unknown.


CONCLUSIONS
Our study suggests that the HCRTR1 gene or a linked locus may modulate the risk for Major Mood Disorders and supports recent studies suggesting an involvement of hypocretin neurotransmitter system in affective disorders.
Neurology II, Department of Neuroscience, University of Turin, Italy. irainero@molinette.piemonte.it
Innocenzo
I
Rainero
Luca
L
Ostacoli
Elisa
E
Rubino
Salvatore
S
Gallone
Luigi Rocco
LR
Picci
Pierpaola
P
Fenoglio
Elisa
E
Negro
Carlo
C
Rosso
Paola
P
De Martino
Mario
M
De Marchi
Pier Maria
PM
Furlan
Lorenzo
L
Pinessi
D000328:Adult; D000368:Aged; D000483:Alleles; D016022:Case-Control Studies; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D019964:Mood Disorders / Q000235:genetics*; D064446:Orexin Receptors; D020641:Polymorphism, Single Nucleotide; D043562:Receptors, G-Protein-Coupled / Q000235:genetics*; D018013:Receptors, Neuropeptide / Q000235:genetics*; D012307:Risk Factors
C578630:HCRTR1 protein, human; D064446:Orexin Receptors; D043562:Receptors, G-Protein-Coupled; D018013:Receptors, Neuropeptide