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| MAO-A and COMT polymorphisms and gene effects in narcolepsy |
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| Author(s): Dauvilliers Y, Neidhart E, Lecendreux M, Billiard M, Tafti M |
| Source: MOLECULAR PSYCHIATRY Volume: 6 Issue: 4 Pages: 367-372 Published: JUL 2001 |
| Times Cited: 44 References: 30 |
| Abstract: Narcolepsy presents one of the tightest associations with a specific HLA antigen (DQB1*0602) but there is strong evidence that non-HLA genes also confer susceptibility. Recent observations have implicated the hypocretin/orexin system in narcolepsy in both humans and animals. In addition, the implication of monoaminergic systems in the pathophysiology of narcolepsy is well established and a significant association between the monoamine oxydase-A (MAO-A) gene and human narcolepsy has recently provided a possible genetic link. We investigated polymorphisms of MAO-A and catechol-O-methyltransferase (COMT) in 97 Caucasians with well-defined narcolepsy-cataplexy and sought for genotypic effects on disease symptoms. No evidence of association between genotype or allele frequencies of both MAO-A or COMB gene and narcolepsy was found. However, a sexual dimorphism and a strong effect of COMB genotype on disease severity were found. Women narcoleptics with high COMB activity fell asleep twice as fast as those with low COMB activity during the multiple sleep latency test (MSLT) while the opposite was true for men. COMB genotype also strongly affected the presence of sleep paralysis and the number of REM sleep onsets during the MSLT. In agreement with well-documented pharmacological results in canine narcolepsy, this study reports the first genetic evidence for the critical involvement of the dopaminergic and/or noradrenergic systems in human narcolepsy. |
| Document Type: Article |
| Language: English |
| Reprint Address: Tafti, M (reprint author), HUG, Belle Idee Biochem & Genet, Chemin Petit Bel Air 2, CH-1225 Chene Bourg, Switzerland |
Addresses:
1. Hop Gul de Chauliac, Montpellier, France
2. Univ Geneva, Dept Psychiat, Unite Biochim & Genet, CH-1211 Geneva 4, Switzerland
3. Hop Robert Debre, F-75019 Paris, France |
| Publisher: NATURE PUBLISHING GROUP, HOUNDMILLS, BASINGSTOKE RG21 6XS, HAMPSHIRE, ENGLAND |
| Subject Category: Biochemistry & Molecular Biology; Neurosciences; Psychiatry |
| IDS Number: 439HG |
| ISSN: 1359-4184 |
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