Association between Alzheimer's Disease and the hypocretin receptor 2 gene

Background: A recent study in animals suggested that hypocretins may play a role in Alzheimer’s disease (AD) promoting the deposition of beta-amyloid. Hypocretins are hypothalamic neuropetides that regulate several physiological functions, like sleep-wake cycle, attention, and feeding. Aims: To investigate the association of polymorphisms in the hypocretin gene system and AD. Methods: A group of 261 Italian AD patients was selected for the study and compared with 261 controls. Cases and controls were genotyped for several SNPs of the HCRT, HCRTR1, and HCRTR2 genes. Results: The genotype and allele distribution of the HCRTR2 G1246A polymorphism varied significantly between patients and controls. Homozygous carriers of the A-allele had an approximately twofold increase in AD risk (OR 1.75;95%CI 1.25 to 2.46; p = 0.0006).No significant difference between the examined characteristics of the disease and different genotypeswas found. Conclusions: This is the first study that examined the association between hypocretin system genes and AD; so our data must be viewed cautiously. We found a significant association between the HCRTR2 gene and AD. Our data support the hypothesis that genetic variations within the HCRTR2 gene are risk factors for AD and may be involved in the disease pathogenesis.