RESUMO
The aim of our study was to investigate whether genetic variants in the hypocretin receptor 1 (HCRTR1) gene could modify the occurrence and the clinical features of migraine. Using a case-control strategy we genotyped 384 migraine patients and 259 controls for three SNPs in the HCRTR1 gene. Genotypic and allelic frequencies of the rs2271933 non-synonymous polymorphism resulted different (χ(2)=9.872, p=0.007; χ(2)=8.108, p=0.004) between migraineurs and controls. The carriage of the A allele was associated with an increased migraine risk (OR 1.42, 95% CI 1.11-1.81). When we divided the migraine patients into different subgroups, the difference reached the level of statistical significance only in migraine without aura. The different genotypes had no significant effect on the examined clinical characteristics of the disease. In conclusion, our data supports the hypothesis that the HCRTR1 gene could represent a genetic susceptibility factor for migraine without aura and suggests that the hypocretin system may have a role in the pathophysiology of migraine.
Assuntos
Predisposição Genética para Doença/genética , Peptídeos e Proteínas de Sinalização Intracelular/fisiologia , Transtornos de Enxaqueca/genética , Neuropeptídeos/fisiologia , Polimorfismo de Nucleotídeo Único/genética , Receptores Acoplados a Proteínas G/genética , Receptores de Neuropeptídeos/genética , Adulto , Estudos de Casos e Controles , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Transtornos de Enxaqueca/metabolismo , Transtornos de Enxaqueca/fisiopatologia , Receptores de Orexina , OrexinasRESUMO
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. LIMITATIONS: 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.
