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

Journal article
Authors I L Bomfim
F Lamb
K Fink
A Szakács
A Silveira
L Franzén
V Azhary
M Maeurer
N Feltelius
Niklas Darin
Tove Hallböök
L Arnheim-Dahlström
I Kockum
T Olsson
Published in Genes and immunity
Volume 18
Pages 75–81
ISSN 1476-5470
Publication year 2017
Published at Institute of Clinical Sciences, Department of Pediatrics
Pages 75–81
Language en
Links dx.doi.org/10.1038/gene.2017.1
www.ncbi.nlm.nih.gov/entrez/query.f...
Subject categories Pediatrics

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.Genes and Immunity advance online publication, 23 March 2017; doi:10.1038/gene.2017.1.

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