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Genes Immun. 2017 Mar;18(2):75-81. doi: 10.1038/gene.2017.1. Epub 2017 Mar 23.

The immunogenetics of narcolepsy associated with A(H1N1)pdm09 vaccination (Pandemrix) supports a potent gene-environment interaction.

Author information

1
Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.
2
Centre for Molecular Medicine, Karolinska University Hospital, Solna, Sweden.
3
Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
4
Department of Neurology, Karolinska University Hospital, Stockholm, Sweden.
5
Department of Pediatrics, Halmstad County Hospital, Halmstad, Sweden.
6
Cardiovascular Medicine Unit, Department of Medicine, Karolinska Institutet, Solna, Sweden.
7
Division of Therapeutic Immunology, Department of Laboratory Medicine, Stockholm, Sweden.
8
Center for Allogeneic Stem Cell Transplantation (CAST), Karolinska University Hospital, Stockholm, Sweden.
9
Medical Products Agency, Uppsala, Sweden.
10
Department of Pediatrics, Institute of Clinical Sciences, University of Gothenburg, Sahlgrenska University Hospital, Gothenburg, Sweden.

Abstract

The influenza A(H1N1)pdm09 vaccination campaign from 2009 to 2010 was associated with a sudden increase in the incidence of narcolepsy in several countries. Narcolepsy with cataplexy is strongly associated with the human leukocyte antigen (HLA) class II DQB1*06:02 allele, and protective associations with the DQB1*06:03 allele have been reported. Several non-HLA gene loci are also associated, such as common variants of the T-cell receptor-α (TRA), the purinergic receptor P2RY11, cathepsin H (CTSH) and TNFSF4/OX40L/CD252. In this retrospective multicenter study, we investigated if these predisposing gene loci were also involved in vaccination-associated narcolepsy. We compared HLA- along with single-nucleotide polymorphism genotypes for non-HLA regions between 42 Pandemrix-vaccinated narcolepsy cases and 1990 population-based controls. The class II gene loci associations supported previous findings. Nominal association (P-value<0.05) with TRA as well as suggestive (P-value<0.1) associations with P2RY11 and CTSH were found. These associations suggest a very strong gene-environment interaction, in which the influenza A(H1N1)pdm09 strain or Pandemrix vaccine can act as potent environmental triggers.

PMID:
28332559
DOI:
10.1038/gene.2017.1
[Indexed for MEDLINE]

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