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.

中文翻译：

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HLA DQB1基因和氨基酸对发作性睡病发展的影响

摘要

介绍

发作性睡病是一种慢性神经系统和自身免疫性遗传性疾病，其特征在于五个主要症状，包括白天过度嗜睡、肌肉张力突然丧失或猝倒、睡眠麻痹、入睡幻觉和夜间睡眠障碍。虽然有几种针对嗜睡症的诊断测试，例如 MSLT（平均睡眠潜伏期测试）、多导睡眠图和脑脊液 (CSF) 中的低范围伪君子，但这些方法的敏感性和特异性还不够。因此，需要对疾病的准确诊断和确认具有更高灵敏度的方法。

方法

根据发作性睡病的罕见患病率，我们安排了一项病例对照关联研究，该研究对 20 名嗜睡症患者和 150 名健康个体进行了采用 SSP-PCR 的高分辨率 HLA 分型程序。

结果

我们的研究表明，对于嗜睡症，DQB1*06:02 等位基因具有最高的易感性，绝对风险为 0.13%（P = 1x10 ^-14，RR = 60.5，PcPPV = 0.13%），而 HLA-DQB1* 03:05等位基因对嗜睡症具有保护作用（P = 1x10 ^-4，PcPPV = 3.19x10 ^-4 %）。此外，AA 分析首次显示位于 DQβ1 链受体 (DQB1 ^{Ser182, Thr185 ) 表位上的 AA 丝氨酸182}和苏氨酸¹⁸⁵对嗜睡症具有显着的易感性 (Pc= 87.03 × 10 ^-13 , PcPPV = 0.024%)而天冬酰胺¹⁸²位于 DQβ1 蛋白受体 (DQB1 ^Asn182) 对发作性睡病的发展具有最高的保护作用（Pc= 2.16 × 10 ^-5，PcPPV = 0.0012%）。

结论

因此，可以提出 HLA 受体表位的多态性差异可能有助于它们与伊朗人群中的嗜睡症的不同关联。