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

Publication ,  Journal Article
Ollila, HM; Ravel, J-M; Han, F; Faraco, J; Lin, L; Zheng, X; Plazzi, G; Dauvilliers, Y; Pizza, F; Hong, S-C; Jennum, P; Knudsen, S; Dong, XS ...
Published in: Am J Hum Genet
January 8, 2015

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.

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Published In

Am J Hum Genet

DOI

EISSN

1537-6605

Publication Date

January 8, 2015

Volume

96

Issue

1

Start / End Page

136 / 146

Location

United States

Related Subject Headings

  • White People
  • Risk Factors
  • Narcolepsy
  • Male
  • Influenza A Virus, H1N1 Subtype
  • Humans
  • Histocompatibility Antigens Class I
  • Haplotypes
  • HLA-DR Antigens
  • HLA-DQ alpha-Chains
 

Citation

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Ollila, H. M., Ravel, J.-M., Han, F., Faraco, J., Lin, L., Zheng, X., … Mignot, E. (2015). HLA-DPB1 and HLA class I confer risk of and protection from narcolepsy. Am J Hum Genet, 96(1), 136–146. https://doi.org/10.1016/j.ajhg.2014.12.010
Ollila, Hanna M., Jean-Marie Ravel, Fang Han, Juliette Faraco, Ling Lin, Xiuwen Zheng, Giuseppe Plazzi, et al. “HLA-DPB1 and HLA class I confer risk of and protection from narcolepsy.Am J Hum Genet 96, no. 1 (January 8, 2015): 136–46. https://doi.org/10.1016/j.ajhg.2014.12.010.
Ollila HM, Ravel J-M, Han F, Faraco J, Lin L, Zheng X, et al. HLA-DPB1 and HLA class I confer risk of and protection from narcolepsy. Am J Hum Genet. 2015 Jan 8;96(1):136–46.
Ollila, Hanna M., et al. “HLA-DPB1 and HLA class I confer risk of and protection from narcolepsy.Am J Hum Genet, vol. 96, no. 1, Jan. 2015, pp. 136–46. Pubmed, doi:10.1016/j.ajhg.2014.12.010.
Ollila HM, Ravel J-M, Han F, Faraco J, Lin L, Zheng X, Plazzi G, Dauvilliers Y, Pizza F, Hong S-C, Jennum P, Knudsen S, Kornum BR, Dong XS, Yan H, Hong H, Coquillard C, Mahlios J, Jolanki O, Einen M, Arnulf I, Högl B, Frauscher B, Crowe C, Partinen M, Huang YS, Bourgin P, Vaarala O, Désautels A, Montplaisir J, Mack SJ, Mindrinos M, Fernandez-Vina M, Mignot E. HLA-DPB1 and HLA class I confer risk of and protection from narcolepsy. Am J Hum Genet. 2015 Jan 8;96(1):136–146.
Journal cover image

Published In

Am J Hum Genet

DOI

EISSN

1537-6605

Publication Date

January 8, 2015

Volume

96

Issue

1

Start / End Page

136 / 146

Location

United States

Related Subject Headings

  • White People
  • Risk Factors
  • Narcolepsy
  • Male
  • Influenza A Virus, H1N1 Subtype
  • Humans
  • Histocompatibility Antigens Class I
  • Haplotypes
  • HLA-DR Antigens
  • HLA-DQ alpha-Chains