Narcolepsy is strongly associated with the T-cell receptor alpha locus
| Autor: | Per Egil Hesla, Thomas Meitinger, Marie Dobrovolna, Sheng Seung-Chul Hong, Pui-Yan Kwok, Birgit Frauscher, William T. Longstreth, Juliane Winkelmann, Alex Desautels, Juliette Faraco, Minae Kawashima, Stacy L. Musone, Mark N. Kvale, Guy A. Rouleau, David Kemlink, Jong-Hyun Jeong, Taku Miyagawa, Makoto Honda, Sung-Pil Lee, Stephanie Hesselson, Christine Erhardt, Pablo V. Gejman, Neil Risch, Christian Gieger, Justin Chen, Patrice Bourgin, Birgit Högl, Geert Mayer, Sona Nevsimalova, Jubao Duan, Ling Lin, Libor Kolesar, Daniel R. Salomon, Joachim Hallmayer, H-Erich Wichmann, Matthew Akana, Mali Einen, Terry Young, Emmanuel Mignot, Jacques Montplaisir, Katsushi Tokunaga, Gerald T. Nepom, Paul E. Peppard, Giuseppe Plazzi, Francesca Poli, Yutaka Honda, Douglas F. Levinson, Thanh G.N. Ton |
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| Přispěvatelé: | Hallmayer J., Faraco J., Lin L., Hesselson S., Winkelmann J., Kawashima M., Mayer G., Plazzi G., Nevsimalova S., Bourgin P., Hong S.S., Honda Y., Honda M., Hogl B., Longstreth W.T. Jr., Montplaisir J., Kemlink D., Einen M., Chen J., Musone S.L., Akana M., Miyagawa T., Duan J., Desautels A., Erhardt C., Hesla P.E., Poli F., Frauscher B., Jeong J.H., Lee S.P., Ton T.G., Kvale M., Kolesar L., Dobrovolnà M., Nepom G.T., Salomon D., Wichmann H.E., Rouleau G.A., Gieger C., Levinson D.F., Gejman P.V., Meitinger T., Young T., Peppard P., Tokunaga K., Kwok P.Y., Risch N., Mignot E. |
| Jazyk: | angličtina |
| Rok vydání: | 2009 |
| Předmět: |
DNA Replication
medicine.medical_specialty Genotype Chromosomes Human Pair 22 Receptors Antigen T-Cell alpha-beta Hypothalamus Locus (genetics) Human leukocyte antigen Biology Polymorphism Single Nucleotide Article Mice 03 medical and health sciences Dogs 0302 clinical medicine Internal medicine Genetics medicine Animals Humans Pandemrix Allele Narcolepsy 030304 developmental biology Chromosomes Human Pair 14 0303 health sciences Sleep disorder Odds ratio medicine.disease 3. Good health Endocrinology 030217 neurology & neurosurgery |
| Zdroj: | Nature genetics |
| Popis: | Narcolepsy with cataplexy, characterized by sleepiness and rapid onset into REM sleep, affects 1 in 2,000 individuals. Narcolepsy was first shown to be tightly associated with HLA-DR2 (ref. 3) and later sublocalized to DQB1*0602 (ref. 4). Following studies in dogs and mice, a 95% loss of hypocretin-producing cells in postmortem hypothalami from narcoleptic individuals was reported. Using genome-wide association (GWA) in Caucasians with replication in three ethnic groups, we found association between narcolepsy and polymorphisms in the TRA@ (T-cell receptor alpha) locus, with highest significance at rs1154155 (average allelic odds ratio 1.69, genotypic odds ratios 1.94 and 2.55, P < 10(-21), 1,830 cases, 2,164 controls). This is the first documented genetic involvement of the TRA@ locus, encoding the major receptor for HLA-peptide presentation, in any disease. It is still unclear how specific HLA alleles confer susceptibility to over 100 HLA-associated disorders; thus, narcolepsy will provide new insights on how HLA-TCR interactions contribute to organ-specific autoimmune targeting and may serve as a model for over 100 other HLA-associated disorders. |
| Databáze: | OpenAIRE |
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