Zhao Wanyu, Zhang Baokun, Yan Zian, Zhao Mengke, Zhang Xiao, Zhang Xiaoyu, Liu Xiaomin, Tang Jiyou
Department of Neurology, The First Affiliated Hospital of Shandong First Medical University, Jinan, Shandong, China.
Department of Neurology, Shandong Qianfoshan Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, China.
Front Neurol. 2024 Apr 25;15:1379723. doi: 10.3389/fneur.2024.1379723. eCollection 2024.
At present, the etiology of narcolepsy is not fully understood, and it is generally believed to be an autoimmune reaction caused by interactions between environmental and genetic factors. Human leukocyte antigen (HLA) class II genes are strongly associated with this gene, especially HLA-DQB10602/DQA10102. In this study, we mainly analyzed the correlation between different genotypes of HLA-DQB10602/DQA10102 and clinical manifestations in Chinese patients with narcolepsy.
Narcolepsy patients who were treated at the Department of Neurology, The First Affiliated Hospital of Shandong First Medical University from January 2021 to September 2023 were selected. General information, sleep monitoring data, cerebrospinal fluid (CSF) orexin levels, and human leukocyte antigen gene typing data were collected. The statistical analysis was performed using SPSS 26.0, and the graphs were drawn using GraphPad Prism 9.5.
A total of 78 patients were included in this study. The DQA1 and DQB1 gene loci were detected in 54 patients, and only the DQB1 gene locus was detected in 24 narcoleptic patients. The most common allele at the HLA-DQB1 locus was 0602 (89.7%), and the most common genotype at this locus was 06020301 (19.2%), followed by 06020602 (17.9%). The most common phenotype of the HLA-DQA1 locus is 0102 (92.6%), and the most common genotype of this locus is 01020102 (27.8%), followed by 01020505 (14.8%). There were significant differences ( < 0.05) between HLA-DQB10602-positive and HLA-DQB10602-negative patients in terms of orexin-A levels, presence or absence of cataplexy, UNS, PSG sleep latency, REM sleep latency, N1 sleep percentage, oxygen depletion index, and average REM latency on the MSLT. The HLA-DQA10102-positive and HLA-DQA10102-negative patients showed significant differences ( < 0.05) in disease course, presence or absence of sudden onset, PSG REM sleep latency, N1 sleep percentage, and average REM latency on the MSLT. There were significant differences in the average REM latency of the MSLT between HLA-DQB10602/DQA10102 homozygous and heterozygous patients < 0.05, and no differences were found in the baseline data, orexin-A levels, scale scores, or other sleep parameters.
Different genotypes of HLA-DQA10102/DQB10602 are associated with symptoms of cataplexy in Chinese narcoleptic patients. Homozygous individuals have a shorter mean REM latency in the MSLT, greater genetic susceptibility, and relatively more severe sleepiness.
目前，发作性睡病的病因尚未完全明确，一般认为是环境因素与遗传因素相互作用引发的自身免疫反应。人类白细胞抗原（HLA）Ⅱ类基因与该病密切相关，尤其是HLA - DQB10602/DQA10102。本研究主要分析中国发作性睡病患者中HLA - DQB10602/DQA10102不同基因型与临床表现之间的相关性。
选取2021年1月至2023年9月在山东第一医科大学第一附属医院神经内科接受治疗的发作性睡病患者。收集一般资料、睡眠监测数据、脑脊液（CSF）食欲素水平及人类白细胞抗原基因分型数据。采用SPSS 26.0进行统计分析，使用GraphPad Prism 9.5绘制图表。
本研究共纳入78例患者。54例患者检测到DQA1和DQB1基因位点，24例发作性睡病患者仅检测到DQB1基因位点。HLA - DQB1位点最常见的等位基因是0602（89.7%），该位点最常见的基因型是06020301（19.2%），其次是06020602（17.9%）。HLA - DQA1位点最常见的表型是0102（92.6%），该位点最常见的基因型是01020102（27.8%），其次是01020505（14.8%）。HLA - DQB10602阳性和HLA - DQB10602阴性患者在食欲素 - A水平、猝倒症的有无、未明睡眠综合征（UNS）、多导睡眠图（PSG）睡眠潜伏期、快速眼动（REM）睡眠潜伏期、N1睡眠百分比、氧耗竭指数以及多次睡眠潜伏期试验（MSLT）的平均REM潜伏期方面存在显著差异（<0.05）。HLA - DQA10102阳性和HLA - DQA10102阴性患者在病程、是否突然起病、PSG REM睡眠潜伏期、N1睡眠百分比以及MSLT的平均REM潜伏期方面存在显著差异（<0.05）。HLA - DQB10602/DQA10102纯合子和杂合子患者在MSLT的平均REM潜伏期方面存在显著差异（<0.05），在基线数据、食欲素 - A水平、量表评分或其他睡眠参数方面未发现差异。
HLA - DQA10102/DQB10602不同基因型与中国发作性睡病患者的猝倒症状相关。纯合子个体在MSLT中的平均REM潜伏期较短，遗传易感性更高，且嗜睡相对更严重。
