Identification of single nucleotide polimorphisms associated with narcolepsy

Narcolepsy is a chronic neurological sleep disorder which is characterized by, excessive daytime sleepiness, cataplexy, hallucinations, sleep paralysis, SOREMPs and disturbed night time sleep. The prevalance is beetween %0,002-%0,18, and it shows difference in diverse populations. Studies revealed that the risk of a first-degree relative of a narcoleptic developing narcolepsy is higher risk (10-40 times) than in the general population, but on the other hand, monozygotic (MZ) twin pairs have been reported with a low concordance. These studies indicate a complex interaction of environmental and genetic factors has been implicated in the etiology of narcolepsy. The pathophysiology of the disorder is stil unknown, recent findings showed a mutation of type 2 hypocretin receptor (Hcrt-2) plays a major role in the etiology of canine narcolepsy. Human narcolepsy is generally not due to Hcrt gene mutations altough profoundly reduced hypocretin levels in cerebrospinal fluid (CSF) and a specific reduction of hypocretin containing neurons has been described. The other studies showed a strong association with HLA DQB1*0602 allele. The present study, SNPs which is thought of susceptible to narcolepsy and mutations in the exons and exon-intron boundries of carnitine palmitoyltransferase 1B (CPTIB) was screened. CPTIB is a key enzyme in the control of beta-oxidation of long-chain fatty acids in the heart and skeletal muscle. PCR amplifications followed by DNA sequence analyses of the regions include SNPs and all exons of the CPT1B which are translated. Thirty narcolepsy patients and 50 healty individuals were included in the study. Some of the exons are sequenced in patient and control groups. Totaly 13 SNPs are revealed. Genotype and allelic frequencies were calculated. Additionaly presence of HLA DQB1*0602 allele in patients with narcolepsy were studied. In study, presented that %90.9 of narcolepsy-cataplexy patients and %14 of control group were positive for HLA DQB1*0602.