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HLA-DPB1 and HLA class I confer risk of and protection from narcolepsy.
Ollila, Hanna M; Ravel, Jean-Marie; Han, Fang; Faraco, Juliette; Lin, Ling; Zheng, Xiuwen; Plazzi, Giuseppe; Dauvilliers, Yves; Pizza, Fabio; Hong, Seung-Chul; Jennum, Poul; Knudsen, Stine; Kornum, Birgitte R; Dong, Xiao Song; Yan, Han; Hong, Heeseung; Coquillard, Cristin; Mahlios, Joshua; Jolanki, Otto; Einen, Mali; Arnulf, Isabelle; Lavault, Sophie; Högl, Birgit; Frauscher, Birgit; Crowe, Catherine; Partinen, Markku; Huang, Yu Shu; Bourgin, Patrice; Vaarala, Outi; Désautels, Alex; Montplaisir, Jacques; Mack, Steven J; Mindrinos, Michael; Fernandez-Vina, Marcelo; Mignot, Emmanuel.
Afiliación
  • Ollila HM; Stanford University Center for Sleep Sciences, Palo Alto, CA 94304, USA.
  • Ravel JM; Stanford University Center for Sleep Sciences, Palo Alto, CA 94304, USA.
  • Han F; Department of Pulmonary Medicine, Peking University People's Hospital, 100044 Beijing, China.
  • Faraco J; Stanford University Center for Sleep Sciences, Palo Alto, CA 94304, USA.
  • Lin L; Stanford University Center for Sleep Sciences, Palo Alto, CA 94304, USA.
  • Zheng X; Department of Biostatistics, University of Washington, PO box 357232, Seattle, WA 98195, USA.
  • Plazzi G; Department of Biomedical and Neuromotor Sciences, University of Bologna, Via Ugo Foscolo 7, 40123 Bologna, Italy; IRCCS Institute of Neurological Sciences, 40139 Bologna, Italy.
  • Dauvilliers Y; INSERM U1061, Reference Center for Narcolepsy, Sleep-Wake Disorders Center, Department of Neurology, Gui-de-Chauliac Hospital, Centre Hospitalier Régional Universitaire Montpellier, 34090 Montpellier, France.
  • Pizza F; Department of Biomedical and Neuromotor Sciences, University of Bologna, Via Ugo Foscolo 7, 40123 Bologna, Italy; IRCCS Institute of Neurological Sciences, 40139 Bologna, Italy.
  • Hong SC; Department of Psychiatry, St. Vincent's Hospital, The Catholic University of Korea, 442-723 Suwon, Korea.
  • Jennum P; Danish Center for Sleep Medicine, Department of Clinical Neurophysiology, University of Copenhagen, Glostrup Hospital, 2600 Glostrup, Denmark.
  • Knudsen S; Norwegian Resource Center for ADHD, TS, and Narcolepsy, Oslo University Hospital, 0450 Ullevål, Norway.
  • Kornum BR; Danish Center for Sleep Medicine, Department of Clinical Neurophysiology, University of Copenhagen, Glostrup Hospital, 2600 Glostrup, Denmark; Molecular Sleep Laboratory, Department of Diagnostics, Glostrup Hospital, 2600 Glostrup, Denmark.
  • Dong XS; Department of Pulmonary Medicine, Peking University People's Hospital, 100044 Beijing, China.
  • Yan H; Department of Pulmonary Medicine, Peking University People's Hospital, 100044 Beijing, China.
  • Hong H; Stanford University Center for Sleep Sciences, Palo Alto, CA 94304, USA.
  • Coquillard C; Department of Pathology, Stanford University School of Medicine, Stanford, CA 94304, USA.
  • Mahlios J; Stanford University Center for Sleep Sciences, Palo Alto, CA 94304, USA.
  • Jolanki O; Stanford University Center for Sleep Sciences, Palo Alto, CA 94304, USA.
  • Einen M; Stanford University Center for Sleep Sciences, Palo Alto, CA 94304, USA.
  • Lavault S; Centre National de Réferénce Narcolepsie et Hypersomnie, 75019 Paris, France.
  • Högl B; Department of Neurology, Medical University of Innsbruck, 6020 Innsbruck, Austria.
  • Frauscher B; Department of Neurology, Medical University of Innsbruck, 6020 Innsbruck, Austria.
  • Crowe C; Mater Private Hospital, Dublin 7, Ireland.
  • Partinen M; Helsinki Sleep Clinic, Vitalmed Research Centre, 00420 Helsinki, Finland; Department of Clinical Neurosciences, University of Helsinki, 00100 Helsinki, Finland.
  • Huang YS; Chang Gung Memorial Hospital and University, Taipei 10591, Taiwan.
  • Bourgin P; Department of Sleep Medicine, Strasbourg University Hospital, Strasbourg University, 67084 Strasbourg, France.
  • Vaarala O; Institute of Clinical Medicine, University of Helsinki, 00100 Helsinki, Finland.
  • Désautels A; Center for Advanced Research in Sleep Medicine, Hôpital du Sacré-Coeur and Department of Neurosciences, University of Montreal, Montreal, QC H3T 1J4, Canada.
  • Montplaisir J; Center for Advanced Research in Sleep Medicine, Hôpital du Sacré-Coeur and Department of Psychiatry, University of Montreal, Montreal QC H3T 1J4, Canada.
  • Mack SJ; Children's Hospital Oakland Research Institute, 5700 Martin Luther King Junior Way, Oakland, CA 94609-1673, USA.
  • Mindrinos M; Stanford Genome Technology Center, Stanford University, Palo Alto, CA 94304, USA.
  • Fernandez-Vina M; Department of Pathology, Stanford University School of Medicine, Stanford, CA 94304, USA.
  • Mignot E; Stanford University Center for Sleep Sciences, Palo Alto, CA 94304, USA. Electronic address: mignot@stanford.edu.
Am J Hum Genet ; 96(1): 136-46, 2015 Jan 08.
Article en En | MEDLINE | ID: mdl-25574827
ABSTRACT
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(∗)0102-DQB1(∗)0602 (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(∗)0103-DPB1(∗)0402 (DP0402; odds ratio [OR] = 0.51 [0.38-0.67], p = 1.01 × 10(-6)) and HLA-DPA1(∗)0103-DPB1(∗)0401 (DP0401; OR = 0.61 [0.47-0.80], p = 2.07 × 10(-4)) and predisposing effects of HLA-DPB1(∗)0501 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(∗)1101 (OR = 1.32 [1.13-1.54], p = 4.92 × 10(-4)), HLA-B(∗)3503 (OR = 1.96 [1.41-2.70], p = 5.14 × 10(-5)), and HLA-B(∗)5101 (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.
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Texto completo: 1 Banco de datos: MEDLINE Asunto principal: Antígenos de Histocompatibilidad Clase I / Cadenas beta de HLA-DP / Narcolepsia Tipo de estudio: Etiology_studies / Incidence_studies / Observational_studies / Risk_factors_studies Límite: Female / Humans / Male Idioma: En Año: 2015 Tipo del documento: Article
Texto completo
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Texto completo: 1 Banco de datos: MEDLINE Asunto principal: Antígenos de Histocompatibilidad Clase I / Cadenas beta de HLA-DP / Narcolepsia Tipo de estudio: Etiology_studies / Incidence_studies / Observational_studies / Risk_factors_studies Límite: Female / Humans / Male Idioma: En Año: 2015 Tipo del documento: Article