Common variants in P2RY11 are associated with narcolepsy

Growing evidence supports the hypothesis that narcolepsy with cataplexy is an autoimmune disease. Using genome-wide association (GWA) in narcolepsy patients versus controls, with replication and fine mapping across three ethnic groups (3406 individuals of European ancestry, 2414 Asians, and 302 Afri...

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Detalles Bibliográficos
Autores principales: Kornum, Birgitte R, Kawashima, Minae, Faraco, Juliette, Lin, Ling, Rico, Tom, Hesselson, Stephanie, Axtell, Robert C, Kuipers, Hedwich, Weiner, Karin, Hamacher, Alexandra, Kassack, Matthias U, Han, Fang, Knudsen, Stine, Li, Jing, Dong, Xiaosong, Winkelmann, Juliane, Plazzi, Giuseppe, Nevsimalova, Sona, Hong, Seung-Chul, Honda, Yutaka, Honda, Makoto, Hogl, Birgit, Ton, Thanh G N, Montplaisir, Jacques, Bourgin, Patrice, Kemlink, David, Huang, Yu-Shu, Warby, Simon, Einen, Mali, Eshragh, Jasmin L, Miyagawa, Taku, Desautels, Alex, Ruppert, Elisabeth, Hesla, Per Egil, Poli, Francesca, Pizza, Fabio, Frauscher, Birgit, Jeong, Jong-Hyun, Lee, Sung-Pil, Strohl, Kingman P, Longstreth, William T, Kvale, Mark, Dobrovolna, Marie, Ohayon, Maurice M, Nepom, Gerald T, Wichmann, H-Erich, Rouleau, Guy A, Gieger, Christian, Levinson, Douglas F, Gejman, Pablo V, Meitinger, Thomas, Peppard, Paul, Young, Terry, Jennum, Poul, Steinman, Lawrence, Tokunaga, Katsushi, Kwok, Pui-Yan, Risch, Neil, Hallmayer, Joachim, Mignot, Emmanuel
Formato: Texto
Lenguaje:English
Publicado: 2010
Materias:
Article
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3019286/
https://www.ncbi.nlm.nih.gov/pubmed/21170044
http://dx.doi.org/10.1038/ng.734
Descripción
Sumario:Growing evidence supports the hypothesis that narcolepsy with cataplexy is an autoimmune disease. Using genome-wide association (GWA) in narcolepsy patients versus controls, with replication and fine mapping across three ethnic groups (3406 individuals of European ancestry, 2414 Asians, and 302 African Americans), we found a novel association between SNP rs2305795 in the 3′UTR of the purinergic receptor subtype 2Y(11) (P2RY11) gene and narcolepsy (p(Mantel Haenszel)=6.1×10(-10); odds ratio 1.28; n=5689). The disease-associated allele is correlated with a 3-fold lower expression of P2RY11 in CD8(+) T lymphocytes (p=0.003) and natural killer (NK) cells (p=0.031) but not in other peripheral blood mononuclear cell (PBMC) types. The low expression variant is also associated with decreased P2RY11 mediated resistance to adenosine triphosphate (ATP) induced cell death in T lymphocytes (p=0.0007) and NK 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.

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