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

Abstract

Introduction 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. Methods 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. Results 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 serine182 and threonine185 located on epitope of DQβ1 chain receptor (DQB1Ser182, Thr185) present significant susceptibility for Narcolepsy (Pc= 87.03 × 10−13, PcPPV = 0.024%) while, asparagine182 located on epitope of DQβ1 protein receptor (DQB1 Asn182 ) confers the highest protection against development of Narcolepsy (Pc= 2.16 × 10−5, PcPPV = 0.0012%). Conclusion 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.