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Sleep Med. 2018 Dec;52:150-157. doi: 10.1016/j.sleep.2018.08.024. Epub 2018 Sep 20.

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.

Author information

1
Clinical Epidemiology and Biometric Unit, IRCCS Policlinico S. Matteo Foundation, viale Golgi 19, 27100, Pavia, Italy.
2
Unit of Sleep Medicine and Epilepsy, IRCCS Mondino Foundation, Pavia, Italy; Department of Brain and Behavioral Sciences, University of Pavia, Pavia, Italy. Electronic address: michele.terzaghi@mondino.it.
3
Scientific Documentation Service, IRCCS Policlinico S. Matteo Foundation, viale Golgi 19, 27100, Pavia, Italy.
4
Department of Transfusion Medicine and Immuno-Hematology (Laboratory of Immunogenetics), IRCCS Policlinico S. Matteo Foundation, viale Golgi 19, 27100, Pavia, Italy.
5
Unit of Sleep Medicine and Epilepsy, IRCCS Mondino Foundation, Pavia, Italy.

Abstract

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-DQB1*06:02 and the worldwide distribution of Narcolepsy type 1 (NT1) and type 2 (NT2); furthermore, we pooled the OR measuring the association between HLA-DQB1*06:02 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-DQB1*06:02 in susceptibility to NT1/NT2 across all ethnicities. HLA-DQB1*06:02 negativity should make clinicians cautious in excluding other diagnoses.

KEYWORDS:

Autoimmunity; Cataplexy; DQB1*06:02; Human Leukocyte Antigens; Narcolepsy

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