Norwegian Centre of Expertise for Neurodevelopmental Disorders and Hypersomnias (NevSom), Department of Rare Disorders, Oslo University Hospital, Ullevål, Norway, Norway.
Institute of Clinical Medicine, University of Oslo, Norway.
Sleep. 2020 Mar 12;43(3). doi: 10.1093/sleep/zsz239.
To explore HLA (human leukocyte antigen) in post-H1N1 narcolepsy type 1 patients (NT1), first-degree relatives and healthy controls, and assess HLA associations with clinical and sleep parameters in patients and first-degree relatives.
Ninety post-H1N1 NT1 patients and 202 of their first-degree relatives were HLA-genotyped (next generation sequencing) and phenotyped (semistructured interviews, Stanford Sleep Questionnaire, polysomnography, and multiple sleep latency test). HLA allele distributions were compared between DQB1*06:02-heterozygous individuals (77 patients, 59 parents, 1230 controls). A subsample (74 patients, 114 relatives) was investigated for associations between HLA-loci and continuous sleep variables using logistic regression. Identified candidate HLA-loci were explored for HLA allele associations with hypnagogic hallucinations and sleep paralysis in 90 patients, and patient allele findings were checked for similar associations in 202 relatives.
DQB106:02 heterozygous post-H1N1 NT1 patients (84.4% H1N1-vaccinated) showed several significant HLA associations similar to those reported previously in samples of mainly sporadic NT1, i.e. DQB103:01, DRB104:01, DRB104:02, DRB104:07, DRB111:04, A25:01, B35:03, and B51:01, and novel associations, i.e. B14:02, C01:02, and C07:01. Parents HLA alleles did not deviate significantly from controls. The HLA-C locus was associated with sleep parameters in patients and relatives. In patients C*02:02 seems to be associated with protective effects against sleep paralysis and hypnagogic hallucinations.
Our findings of similar risk/protective HLA-alleles in post-H1N1 as in previous studies of mainly sporadic narcolepsy support similar disease mechanisms. We also report novel allelic associations. Associations between HLA-C and sleep parameters were seen independent of NT1 diagnosis, supporting involvement of HLA-C in sleep subphenotypes.
探索人白细胞抗原（HLA）在甲型 H1N1 后发作的 1 型发作性睡病（NT1）患者、一级亲属和健康对照者中的作用，并评估 HLA 与患者和一级亲属的临床和睡眠参数的相关性。
对 90 例甲型 H1N1 后 NT1 患者和 202 例一级亲属进行 HLA 基因分型（下一代测序）和表型分析（半结构式访谈、斯坦福睡眠问卷、多导睡眠图和多次睡眠潜伏期试验）。比较 DQB1*06:02 杂合子个体（77 例患者、59 例父母、1230 例对照）之间的 HLA 等位基因分布。对一个亚样本（74 例患者、114 例亲属）使用逻辑回归研究 HLA 基因座与连续睡眠变量之间的关系。在 90 例患者中，对确定的候选 HLA 基因座与催眠幻觉和睡眠瘫痪的 HLA 等位基因相关性进行了研究，并在 202 例亲属中检查了患者等位基因的类似相关性。
甲型 H1N1 后 NT1 患者（84.4%接种过 H1N1 疫苗）中 DQB106:02 杂合子患者出现了多个与先前在主要散发 NT1 样本中报告的相似的 HLA 相关性，即 DQB103:01、DRB104:01、DRB104:02、DRB104:07、DRB111:04、A25:01、B35:03 和 B51:01，以及新的相关性，即 B14:02、C01:02 和 C07:01。父母的 HLA 等位基因与对照组相比没有明显差异。HLA-C 基因座与患者和亲属的睡眠参数相关。在患者中，C*02:02 似乎与睡眠瘫痪和催眠幻觉的保护作用有关。
我们在甲型 H1N1 后发作的患者中发现与先前主要散发的发作性睡病研究中相似的风险/保护 HLA 等位基因，支持类似的发病机制。我们还报告了新的等位基因相关性。HLA-C 与睡眠参数之间的相关性独立于 NT1 诊断，支持 HLA-C 参与睡眠亚表型。
