HLA-DQB1*06:02 与伴或不伴猝倒的发作性睡病的相关性：在四大种族群体中验证一种安全且敏感的遗传检测方法。系统荟萃分析。
Correlation between HLA-DQB1*06:02 and narcolepsy with and without cataplexy: approving a safe and sensitive genetic test in four major ethnic groups. A systematic meta-analysis.
机构信息
Clinical Epidemiology and Biometric Unit, IRCCS Policlinico S. Matteo Foundation, viale Golgi 19, 27100, Pavia, Italy.
Unit of Sleep Medicine and Epilepsy, IRCCS Mondino Foundation, Pavia, Italy; Department of Brain and Behavioral Sciences, University of Pavia, Pavia, Italy.
出版信息
Sleep Med. 2018 Dec;52:150-157. doi: 10.1016/j.sleep.2018.08.024. Epub 2018 Sep 20.
STUDY OBJECTIVES
we performed a meta-analysis to assess the usefulness of HLA testing for Narcolepsy diagnosis in four major ethnical groups: Asians, Afro-Americans, Amerindians and Caucasians.
METHODS
PubMed, EMBASE, Web of Science, Scopus and Cochrane databases were searched for articles in English and French published before October 2017 on HLA class II alleles in Narcolepsy. We included case-control studies, cross-sectional and retrospective cohort studies with patients diagnosed following the International classifications of sleep disorders (1990-2012) and ethnically matched controls. Following PRISMA guidelines, two investigators independently extracted data according to the inclusion criteria listed in PROSPERO CRD42017058677. A third researcher was consulted for discrepancies. We extracted and pooled adjusted OR using random-effect models. We verified the strength of the association between HLA-DQB106:02 and the worldwide distribution of Narcolepsy type 1 (NT1) and type 2 (NT2); furthermore, we pooled the OR measuring the association between HLA-DQB106:02 and NT1, NT2 and hypersomniacs.
RESULTS
We identified 511 titles. Of these, 12 case-control studies were included, for a total of 2077 NT1 patients, 235 NT2 patients, 161 hypersomniacs and 7802 controls. In the population-stratified analysis, HLA-DQB1*06:02 conferred an increased risk for NT1 (OR: 24.1, IC: 14.6-39.5, p < 0.001) and NT2 (OR: 3.9; IC: 2.2-6.8, p < 0.001). For NT1 the pooled estimated positive Likelihood Ratio (LR+) was 5.94 (IC: 3.71-9.51) and the negative Likelihood Ratio (LR-) was 0.23 (IC: 0.16-0.33); for NT2 LR+ was 3.35 (IC: 2.08-5.38) and LR- 0.72 (IC: 0.63-0.81). Moreover, for hypersomniacs LR+ was 1.436 (IC 0.668-3.089) and LR- 0.903 (IC 0.714-1.142).
CONCLUSIONS
Our data support the preponderant role of HLA-DQB106:02 in susceptibility to NT1/NT2 across all ethnicities. HLA-DQB106:02 negativity should make clinicians cautious in excluding other diagnoses.
研究目的
我们进行了一项荟萃分析，以评估 HLA 检测在四个主要种族（亚洲人、非裔美国人、美洲印第安人和高加索人）中对嗜睡症诊断的有用性。
方法
检索了 PubMed、EMBASE、Web of Science、Scopus 和 Cochrane 数据库中关于嗜睡症中 HLA Ⅱ类等位基因的英文和法文出版物，检索时间截至 2017 年 10 月。我们纳入了病例对照研究、横断面和回顾性队列研究，这些研究的患者均按照国际睡眠障碍分类（1990-2012 年）进行了诊断，并与种族匹配的对照组进行了比较。根据 PROSPERO CRD42017058677 列出的纳入标准，两名研究人员独立提取数据。对于有分歧的研究，我们咨询了第三位研究人员。我们使用随机效应模型提取和汇总了校正后的 OR。我们验证了 HLA-DQB106:02 与嗜睡症 1 型（NT1）和 2 型（NT2）在全球分布之间的关联强度；此外，我们还汇总了 HLA-DQB106:02 与 NT1、NT2 和嗜睡症患者之间关联的 OR。
结果
我们确定了 511 个标题。其中，纳入了 12 项病例对照研究，共纳入了 2077 名 NT1 患者、235 名 NT2 患者、161 名嗜睡症患者和 7802 名对照组。在人群分层分析中，HLA-DQB1*06:02 增加了 NT1（OR：24.1，95%置信区间：14.6-39.5，p<0.001）和 NT2（OR：3.9；95%置信区间：2.2-6.8，p<0.001）的患病风险。对于 NT1，汇总的估计阳性似然比（LR+）为 5.94（95%置信区间：3.71-9.51），阴性似然比（LR-）为 0.23（95%置信区间：0.16-0.33）；对于 NT2，LR+为 3.35（95%置信区间：2.08-5.38），LR-为 0.72（95%置信区间：0.63-0.81）。此外，对于嗜睡症患者，LR+为 1.436（95%置信区间：0.668-3.089），LR-为 0.903（95%置信区间：0.714-1.142）。
结论
我们的数据支持 HLA-DQB106:02 在所有种族中对 NT1/NT2 易感性的主要作用。HLA-DQB106:02 阴性应使临床医生在排除其他诊断时保持谨慎。
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