Narcolepsy is a disabling and prevalent sleep disorder affecting 0.05-0.1 percent of the general population. Predisposition to human narcolepsy involves both genetic and environmental factors. Previous studies have shown that one of the genetic susceptibility factors involved is the Human Leukocyte (HLA) allele DQB1*0602. This allele however only accounts for a small portion of the overall genetic predisposition. (1) The first aim of this competing continuation application will be to refine our current understanding of HLA associations in narcolepsy. Preliminary data suggest that multiple HLA alleles as opposed to a single allele (e.g. DQB1*0602) have significant effects on disease predisposition. These data will be confirmed and the work will be extended to study HLA complex loci other than HLA-DQ. We anticipate that the results of this study will facilitate the use of HLA typing as a diagnostic tool and will allow us to estimate the contribution of the entire HLA complex (as opposed to a single HLA allele) to narcolepsy susceptibility. (2) A second aim will be to study genetic markers syntenic to the canine narcolepsy gene locus using previously identified multiplex families and singleton families. (3) Candidate genes in the area of immunology and neurochemistry will also be studied using an association-based design as part of the third specific aim. We anticipate that this proposal will allow us to identify novel narcolepsy genetic factors, some of which might also be fundamentally involved in sleep regulation.
| Hallmayer, Joachim; Faraco, Juliette; Lin, Ling et al. (2009) Narcolepsy is strongly associated with the T-cell receptor alpha locus. Nat Genet 41:708-11 |
| Hong, Seung-Chul; Lin, Ling; Lo, Betty et al. (2007) DQB1*0301 and DQB1*0601 modulate narcolepsy susceptibility in Koreans. Hum Immunol 68:59-68 |
| Mignot, Emmanuel; Nishino, Seiji (2005) Emerging therapies in narcolepsy-cataplexy. Sleep 28:754-63 |
| Nishino, S; Kanbayashi, T; Fujiki, N et al. (2003) CSF hypocretin levels in Guillain-Barre syndrome and other inflammatory neuropathies. Neurology 61:823-5 |
| Salomon, Ronald M; Ripley, Beth; Kennedy, John S et al. (2003) Diurnal variation of cerebrospinal fluid hypocretin-1 (Orexin-A) levels in control and depressed subjects. Biol Psychiatry 54:96-104 |
| Vankova, Jitka; Stepanova, Iva; Jech, Robert et al. (2003) Sleep disturbances and hypocretin deficiency in Niemann-Pick disease type C. Sleep 26:427-30 |
| Mignot, Emmanuel; Lammers, Gert Jan; Ripley, Beth et al. (2002) The role of cerebrospinal fluid hypocretin measurement in the diagnosis of narcolepsy and other hypersomnias. Arch Neurol 59:1553-62 |
| Hong, Seung-Chul; Leen-Kim; Park, Soo-A et al. (2002) HLA and hypocretin studies in Korean patients with narcolepsy. Sleep 25:440-4 |
| Okun, Michele L; Lin, Ling; Pelin, Zerrin et al. (2002) Clinical aspects of narcolepsy-cataplexy across ethnic groups. Sleep 25:27-35 |
| Hungs, M; Mignot, E (2001) Hypocretin/orexin, sleep and narcolepsy. Bioessays 23:397-408 |
Showing the most recent 10 out of 37 publications
