HLA-DPB1 and HLA Class I Confer Risk of and Protection from Narcolepsy - Université de Montpellier Accéder directement au contenu
Article Dans Une Revue American Journal of Human Genetics Année : 2015

HLA-DPB1 and HLA Class I Confer Risk of and Protection from Narcolepsy

Hanna m. Ollila
  • Fonction : Auteur
Jean-Marie Ravel
Fang Han
  • Fonction : Auteur
  • PersonId : 1033407
Juliette Faraco
  • Fonction : Auteur
Ling Lin
Xiuwen Zheng
  • Fonction : Auteur
Seung-Chul Hong
  • Fonction : Auteur
Poul Jennum
  • Fonction : Auteur
Birgit Kornum
  • Fonction : Auteur
Xiao Song Dong
  • Fonction : Auteur
Han Yan
  • Fonction : Auteur
  • PersonId : 772489
  • IdRef : 184949912
Heeseung Hong
  • Fonction : Auteur
Cristin Coquillard
  • Fonction : Auteur
Joshua Mahlios
  • Fonction : Auteur
Otto Jolanki
  • Fonction : Auteur
Mali Einen
  • Fonction : Auteur
Catherine Crowe
  • Fonction : Auteur
Markku Partinen
Yu Shu Huang
  • Fonction : Auteur
Outi Vaarala
  • Fonction : Auteur
Alex Desautels
Jacques Montplaisir
  • Fonction : Auteur
  • PersonId : 841537
Steven Mack
  • Fonction : Auteur
Michael Mindrinos
  • Fonction : Auteur
Marcelo Fernandez-Vina
  • Fonction : Auteur
Emmanuel Jean Marie Mignot
  • Fonction : Auteur

Résumé

Type 1 narcolepsy, a disorder caused by a lack of hypocretin (orexin), is so strongly associated with human leukocyte antigen (HLA) class II HLA-DQA1(∗)01:02-DQB1(∗)06:02 (DQ0602) that very few non-DQ0602 cases have been reported. A known triggering factor for narcolepsy is pandemic 2009 influenza H1N1, suggesting autoimmunity triggered by upper-airway infections. Additional effects of other HLA-DQ alleles have been reported consistently across multiple ethnic groups. Using over 3,000 case and 10,000 control individuals of European and Chinese background, we examined the effects of other HLA loci. After careful matching of HLA-DR and HLA-DQ in case and control individuals, we found strong protective effects of HLA-DPA1(∗)01:03-DPB1(∗)04:02 (DP0402; odds ratio [OR] = 0.51 [0.38-0.67], p = 1.01 × 10(-6)) and HLA-DPA1(∗)01:03-DPB1(∗)04:01 (DP0401; OR = 0.61 [0.47-0.80], p = 2.07 × 10(-4)) and predisposing effects of HLA-DPB1(∗)05:01 in Asians (OR = 1.76 [1.34-2.31], p = 4.71 × 10(-05)). Similar effects were found by conditional analysis controlling for HLA-DR and HLA-DQ with DP0402 (OR = 0.45 [0.38-0.55] p = 8.99 × 10(-17)) and DP0501 (OR = 1.38 [1.18-1.61], p = 7.11 × 10(-5)). HLA-class-II-independent associations with HLA-A(∗)11:01 (OR = 1.32 [1.13-1.54], p = 4.92 × 10(-4)), HLA-B(∗)35:03 (OR = 1.96 [1.41-2.70], p = 5.14 × 10(-5)), and HLA-B(∗)51:01 (OR = 1.49 [1.25-1.78], p = 1.09 × 10(-5)) were also seen across ethnic groups in the HLA class I region. These effects might reflect modulation of autoimmunity or indirect effects of HLA class I and HLA-DP alleles on response to viral infections such as that of influenza.

Dates et versions

hal-02137019 , version 1 (22-05-2019)

Identifiants

Citer

Hanna m. Ollila, Jean-Marie Ravel, Fang Han, Juliette Faraco, Ling Lin, et al.. HLA-DPB1 and HLA Class I Confer Risk of and Protection from Narcolepsy. American Journal of Human Genetics, 2015, 96 (1), pp.136-146. ⟨10.1016/j.ajhg.2014.12.010⟩. ⟨hal-02137019⟩
70 Consultations
0 Téléchargements

Altmetric

Partager

Gmail Mastodon Facebook X LinkedIn More