人类白细胞抗原II类-DR-DQ与发作性睡病之间的关联：一项病例对照研究。

Association between human leukocyte antigen class II-DR-DQ and narcolepsy: a case control study.

作者信息

Bacelar Andrea, Fernandez Oscar, Paradella Eduardo, Rodrigues Raimundo Nonato, de Castro Moreno Claudia Roberta, Alvarenga Regina

机构信息

Department of Neurology, Federal University of the State of Rio de Janeiro, Rio de Janeiro, Brazil.

Genetic Lab in Carlos Haya University Hospital, Málaga, Spain.

出版信息

J Clin Sleep Med. 2024 Dec 1;20(12):1945-1953. doi: 10.5664/jcsm.11300.

DOI:10.5664/jcsm.11300

PMID:39150697

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11609832/

Abstract

STUDY OBJECTIVES

Narcolepsy is a neurologic disorder characterized by irresistible sleep attacks. Although its etiology is unknown, it is strongly associated with genetic variances in the human leukocyte antigen (HLA) complex. We investigated the association of HLA class II-DR-DQ alleles in a sample of patients with narcolepsy-cataplexy (narcolepsy type 1 [NT1]) and patients with narcolepsy without cataplexy (narcolepsy type 2) with a control group. Additionally, we compared demographic, clinical, and laboratory characteristics of patients with narcolepsy with or without the allele.

METHODS

This case control study included 21 patients with NT1 (56.8%), 16 patients with narcolepsy type 2 (43.2%), and 100 controls. Sequence-based typing identified HLA- alleles, and HLA- typing was done using polymerase chain reaction (PCR)-sequence-specific oligonucleotide. Allele and haplotype frequencies were calculated by direct counting. Nocturnal polysomnography and Multiple Sleep Latency Test were performed in all participants.

RESULTS

In the NT1 group, only 1 allele had a significantly higher frequency than in the narcolepsy type 2 group: (61.9% vs 18.8%). Compared to controls, (61.9% vs 18.0% in controls) and (47.6% vs 8.0%), had higher frequencies in patients with NT1. Multiple analyses showed that patients with NT1 had an increased chance of being HLA- positive. HLA- haplotype is associated with NT1 in our Brazilian patients. Polysomnography was identified in positive subgroup rapid eye movement sleep latency ≤ 15 minutes, and all patients had 2 or more sleep-onset rapid eye movement periods at Multiple Sleep Latency Test.

CONCLUSIONS

This study showed a strong association between HLA- and the haplotype HLA- in patients with NT1. Patients with allele showed shorter rapid eye movement sleep latencies at polysomnography. These results reinforce the suggestion of genotyping as relevant to narcolepsy screening.

CITATION

Bacelar A, Fernandez O, Paradella E, Rodrigues RN, de Castro Moreno CR, Alvarenga R. Association between human leukocyte antigen class II-DR-DQ and narcolepsy: a case control study. . 2024;20(12):1945-1953.

摘要

研究目的

发作性睡病是一种以不可抗拒的睡眠发作为特征的神经系统疾病。尽管其病因尚不清楚，但它与人类白细胞抗原（HLA）复合体中的基因变异密切相关。我们在发作性睡病伴猝倒（发作性睡病1型[NT1]）患者样本和无猝倒的发作性睡病（发作性睡病2型）患者样本与一个对照组中，研究了HLA II类-DR-DQ等位基因的关联。此外，我们比较了有或无该等位基因的发作性睡病患者的人口统计学、临床和实验室特征。

方法

这项病例对照研究纳入了21例NT1患者（56.8%）、16例发作性睡病2型患者（43.2%）和100名对照。基于序列的分型确定了HLA等位基因，HLA分型使用聚合酶链反应（PCR）-序列特异性寡核苷酸进行。等位基因和单倍型频率通过直接计数计算。对所有参与者进行了夜间多导睡眠图和多次睡眠潜伏期测试。

结果

在NT1组中，只有1个等位基因的频率显著高于发作性睡病2型组：（61.9%对18.8%）。与对照组相比，（对照组中为18.0%对NT1患者中的61.9%）和（对照组中为8.0%对NT1患者中的47.6%）在NT1患者中的频率更高。多项分析表明，NT1患者HLA阳性的几率增加。在我们的巴西患者中，HLA单倍型与NT1相关。在阳性亚组中通过多导睡眠图确定快速眼动睡眠潜伏期≤15分钟，并且所有患者在多次睡眠潜伏期测试中有2次或更多次睡眠起始快速眼动期。