Center for Neuropsychiatric Research, National Health Research Institutes, Zhunan, Taiwan.
Sleep Med. 2013 Dec;14(12):1393-7. doi: 10.1016/j.sleep.2013.06.017. Epub 2013 Sep 29.
Narcolepsy is a rare, chronic, disabling neuropsychiatric disorder characterized by excessive daytime sleepiness, cataplexy, hypnagogic hallucinations, sleep paralysis, and abnormal rapid eye movement sleep. It is strongly associated with the HLA-DQB1(∗)06:02 allele in various ethnic groups. Our study aimed to investigate the allelic spectrum of HLA-DQB1 in a sample of Han Chinese patients with narcolepsy and control subjects from Taiwan.
We determined the genotype of the major histocompatibility complex, class II, DQ β1 gene, HLA-DQB1, in 72 narcolepsy subjects (44 men, 28 women), including 52 narcolepsy subjects with cataplexy (narcolepsy+cataplexy), 20 narcolepsy subjects without cataplexy (narcolepsy-cataplexy), and 194 control subjects (94 men, 100 women) using a sequence-specific oligonucleotide-probe hybridization technique.
We found a strong HLA-DQB1(∗)06:02 association in narcolepsy+cataplexy subjects (odds ratio [OR], 321.4 [95% confidence interval {CI}, 70.7-1461.4]). The association was less prominent in narcolepsy-cataplexy subjects (OR, 6.9 [95% CI, 2.4-20.1]). In addition to the DQB1(∗)06:02, we found that (∗)03:01 also was a predisposing allele (OR, 2.0 [95% CI, 1.1-3.7]) in narcolepsy+cataplexy subjects, though the (∗)06:01 was a predisposing allele (OR, 2.8 [95% CI, 1.2-6.7]) in narcolepsy-cataplexy subjects. Furthermore, we found a significant overrepresentation of DQB1(∗)06:02 homozygotes in narcolepsy+cataplexy subjects.
Our data add further support to the strong association of the HLA-DQB1(∗)06:02 allele with narcolepsy, especially in narcolepsy+cataplexy patients. Our study also indicates additional HLA-DQB1 alleles may modify the presentation of narcolepsy+cataplexy patients, such as DQB1(∗)03:01 and DQB1(∗)06:01 in our study. Our results are limited by the small sample size and can only be considered as preliminary findings.
发作性睡病是一种罕见的、慢性的、使人致残的神经精神疾病，其特征是白天过度嗜睡、猝倒、催眠幻觉、睡眠瘫痪和异常的快速眼动睡眠。它与 HLA-DQB1(∗)06:02 等位基因在不同种族中密切相关。我们的研究旨在调查 HLA-DQB1 在台湾汉族发作性睡病患者和对照组中的等位基因谱。
我们使用序列特异性寡核苷酸探针杂交技术，在 72 名发作性睡病患者（44 名男性，28 名女性），包括 52 名有猝倒的发作性睡病患者（发作性睡病+猝倒），20 名无猝倒的发作性睡病患者（发作性睡病-猝倒）和 194 名对照组（94 名男性，100 名女性）中确定了主要组织相容性复合体、Ⅱ类、DQβ1 基因 HLA-DQB1 的基因型。
我们发现发作性睡病+猝倒患者中 HLA-DQB1(∗)06:02 存在强烈的关联（优势比[OR]，321.4[95%置信区间{CI}，70.7-1461.4]）。在发作性睡病-猝倒患者中，这种关联不太明显（OR，6.9[95%CI，2.4-20.1]）。除了 DQB1(∗)06:02 外，我们还发现（∗）03:01 也是发作性睡病+猝倒患者的易感等位基因（OR，2.0[95%CI，1.1-3.7]），而（∗）06:01 是发作性睡病-猝倒患者的易感等位基因（OR，2.8[95%CI，1.2-6.7]）。此外，我们发现发作性睡病+猝倒患者中 DQB1(∗)06:02 纯合子的比例显著升高。
我们的数据进一步支持 HLA-DQB1(∗)06:02 等位基因与发作性睡病的强烈关联，特别是在发作性睡病+猝倒患者中。我们的研究还表明，其他 HLA-DQB1 等位基因可能会改变发作性睡病+猝倒患者的表现，例如我们研究中的 DQB1(∗)03:01 和 DQB1(∗)06:01。我们的结果受到样本量小的限制，只能被认为是初步发现。
