Common variants in P2RY11 are associated with narcolepsy View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2011-01

AUTHORS

Birgitte R Kornum, Minae Kawashima, Juliette Faraco, Ling Lin, Thomas J Rico, Stephanie Hesselson, Robert C Axtell, Hedwich Kuipers, Karin Weiner, Alexandra Hamacher, Matthias U Kassack, Fang Han, Stine Knudsen, Jing Li, Xiaosong Dong, Juliane Winkelmann, Giuseppe Plazzi, Sona Nevsimalova, Seung-Chul Hong, Yutaka Honda, Makoto Honda, Birgit Högl, Thanh G N Ton, Jacques Montplaisir, Patrice Bourgin, David Kemlink, Yu-Shu Huang, Simon Warby, Mali Einen, Jasmin L Eshragh, Taku Miyagawa, Alex Desautels, Elisabeth Ruppert, Per Egil Hesla, Francesca Poli, Fabio Pizza, Birgit Frauscher, Jong-Hyun Jeong, Sung-Pil Lee, Kingman P Strohl, William T Longstreth, Mark Kvale, Marie Dobrovolna, Maurice M Ohayon, Gerald T Nepom, H-Erich Wichmann, Guy A Rouleau, Christian Gieger, Douglas F Levinson, Pablo V Gejman, Thomas Meitinger, Paul Peppard, Terry Young, Poul Jennum, Lawrence Steinman, Katsushi Tokunaga, Pui-Yan Kwok, Neil Risch, Joachim Hallmayer, Emmanuel Mignot

ABSTRACT

Growing evidence supports the hypothesis that narcolepsy with cataplexy is an autoimmune disease. We here report genome-wide association analyses for narcolepsy with replication and fine mapping across three ethnic groups (3,406 individuals of European ancestry, 2,414 Asians and 302 African Americans). We identify a SNP in the 3' untranslated region of P2RY11, the purinergic receptor subtype P2Y₁₁ gene, which is associated with narcolepsy (rs2305795, combined P = 6.1 × 10⁻¹⁰, odds ratio = 1.28, 95% CI 1.19-1.39, n = 5689). The disease-associated allele is correlated with reduced expression of P2RY11 in CD8(+) T lymphocytes (339% reduced, P = 0.003) and natural killer (NK) cells (P = 0.031), but not in other peripheral blood mononuclear cell types. The low expression variant is also associated with reduced P2RY11-mediated resistance to ATP-induced cell death in T lymphocytes (P = 0.0007) and natural killer cells (P = 0.001). These results identify P2RY11 as an important regulator of immune-cell survival, with possible implications in narcolepsy and other autoimmune diseases. More... »

PAGES

66

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/ng.734

DOI

http://dx.doi.org/10.1038/ng.734

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1005250736

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/21170044


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