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

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 DQB1*06:02 allele.

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-DRB1 alleles, and HLA-DQB1 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.

In the NT1 group, only 1 allele had a significantly higher frequency than in the narcolepsy type 2 group: DQB1*06:02 (61.9% vs 18.8%). Compared to controls, DQB1*06:02 (61.9% vs 18.0% in controls) and DRB1*15:01 (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-DQB1*06:02 positive. HLA-DRB1*15:01-DQA1*01:02-DQB1*06:02 haplotype is associated with NT1 in our Brazilian patients. Polysomnography was identified in DQB1*06:02 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.

This study showed a strong association between HLA-DQB1*06:02 and the haplotype HLA-DRB1*15:01-DQA1*01:02-DQB1*06:02 in patients with NT1. Patients with DQB1*0602 allele showed shorter rapid eye movement sleep latencies at polysomnography. These results reinforce the suggestion of DQB1 genotyping as relevant to narcolepsy screening.

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. J Clin Sleep Med. 2024;20(12):1945-1953.