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Narcolepsy is a chronic neurological and a genetic disorder of autoimmune origin, which is characterized by five main symptoms, including excessive day time sleepiness, sudden loss of muscle tone or cataplexy, sleep paralysis, hypnagogic hallucinations, and disturbed nocturnal sleep. While there are several diagnostic tests for Narcolepsy such as MSLT (mean sleep latency test), polysomnography and low range of hypocretin in cerebrospinal fluid (CSF), sensitivity and specificity in these methodologies are not sufficient enough. Therefore, methods with higher sensitivity for the accurate diagnosis and confirmation of the disease are necessary. According to the infrequent prevalence of narcolepsy disease, we scheduled a case-control association study with 20 narcoleptic patients and 150 healthy individuals in a high-resolution HLA typing procedure employing SSP-PCR. Our study demonstrates that the DQB1*06:02 allele provides the highest susceptibility with absolute risk of 0.13%, for Narcolepsy (P = 1x10 −14 , RR = 60.5, PcPPV = 0.13%), while, HLA-DQB1* 03:05 allele presents protection to Narcolepsy (P = 1x10 −4 , PcPPV = 3.19x10 −4 %). Furthermore, for the first time, the AA analysis displayed that AA serine 182  and threonine 185  located on epitope of DQβ1 chain receptor (DQB1 Ser182,Thr185 ) present significant susceptibility for Narcolepsy (Pc= 87.03 × 10 −13 , PcPPV = 0.024%) while, asparagine 182  located on epitope of DQβ1 protein receptor (DQB1Asn182) confers the highest protection against development of Narcolepsy (Pc= 2.16 × 10 −5 , PcPPV = 0.0012%). Thus, this can be proposed that the polymorphic differences in the epitope of the HLA receptor could contribute to their differential association with the Narcolepsy in Iranian population.

The impact of the HLA DQB1 gene and amino acids on the development of narcolepsy