RGD Reference Report - HLA-DPB1 and HLA class I confer risk of and protection from narcolepsy. - Rat Genome Database

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HLA-DPB1 and HLA class I confer risk of and protection from narcolepsy.

Authors: 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  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 
Citation: Ollila HM, etal., Am J Hum Genet. 2015 Jan 8;96(1):136-46. doi: 10.1016/j.ajhg.2014.12.010.
RGD ID: 150429810
Pubmed: PMID:25574827   (View Abstract at PubMed)
PMCID: PMC4289679   (View Article at PubMed Central)
DOI: DOI:10.1016/j.ajhg.2014.12.010   (Journal Full-text)

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.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
narcolepsy susceptibilityIAGP 150429810DNA:polymorphisms and haplotypes: :multiple (human)RGD 

Phenotype Annotations    Click to see Annotation Detail View

Manual Human Phenotype Annotations - RGD

TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
Narcolepsy susceptibilityIAGP 150429810DNA:polymorphisms and haplotypes: :multiple RGD 
Objects Annotated

Genes (Homo sapiens)
HLA-DPB1  (major histocompatibility complex, class II, DP beta 1)


Additional Information