MAO-A and COMT polymorphisms and gene effects in narcolepsy.

Details

Serval ID
serval:BIB_1456CDA544E6
Type
Article: article from journal or magazin.
Collection
Publications
Title
MAO-A and COMT polymorphisms and gene effects in narcolepsy.
Journal
Molecular Psychiatry
Author(s)
Dauvilliers Y., Neidhart E., Lecendreux M., Billiard M., Tafti M.
ISSN
1359-4184[print], 1359-4184[linking]
Publication state
Published
Issued date
07/2001
Volume
6
Number
4
Pages
367-372
Language
english
Notes
Publication types: Comparative Study ; Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
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 COMT gene and narcolepsy was found. However, a sexual dimorphism and a strong effect of COMT genotype on disease severity were found. Women narcoleptics with high COMT activity fell asleep twice as fast as those with low COMT activity during the multiple sleep latency test (MSLT) while the opposite was true for men. COMT 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.
Keywords
Cataplexy/enzymology, Cataplexy/genetics, Catechol O-Methyltransferase/genetics, DNA/blood, European Continental Ancestry Group/genetics, Female, France, Genotype, Humans, Introns, Isoenzymes/genetics, Male, Minisatellite Repeats, Monoamine Oxidase/genetics, Narcolepsy/enzymology, Narcolepsy/genetics, Polymerase Chain Reaction, Polymorphism, Genetic, Reference Values, Sex Characteristics, Sleep/physiology, Sleep, REM
Pubmed
Web of science
Open Access
Yes
Create date
24/01/2008 15:55
Last modification date
20/08/2019 12:43
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