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 (DQB1^{Ser182,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.

Keywords:

• Sleep
• narcolepsy
• HLA-DQB1
• polymerase chain reaction
• sequence-specific primers

Compliance with ethical standards

This study was certified by the ethics committee and review board of the Tehran University of Medical Sciences.

Consent to participate

Questionnaire forms were prepared for each patient and control individuals. Before being included in the study, informed consent was taken from all the patients, or their legal guardians and control subjects.

Acknowledgements

We gratefully acknowledge patients with AD and healthy volunteers who participated in this study.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Additional information

Funding

This study was supported by a research grant from Tehran University of Medical Sciences [grant numbers 96-02-30-33243].