HLA and sleep parameter associations in post-H1N1 narcolepsy type 1 patients and first-degree relatives
Hilde T. Juvodden, Marte K. Viken, Sebjørg E. H. Nordstrand, Rannveig Viste, Lars T. Westlye, Per M. Thorsby, Benedicte A. Li, Stine Knudsen-Heier
Studien er publisert i SLEEP
STUDY OBJECTIVES: 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.
METHODS: Ninety post-H1N1 NT1 patients and 202 of their first-degree relatives were HLA-genotyped (next generation sequencing) and phenotyped (semi-structured interviews, Stanford Sleep Questionnaire, polysomnography, 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.
RESULTS: DQB1*06:02 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. DQB1*03:01, DRB1*04:01, DRB1*04:02, DRB1*04:07, DRB1*11:04, A*25:01, B*35:03 and B*51:01, and novel associations i.e. B*14:02, C*01:02 and C*07:01. 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.
CONCLUSION: 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.