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MAO-A and COMT polymorphisms and gene effects in narcolepsy

Molecular Psychiatry volume 6, pages 367–372 (2001)Cite this article

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.

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Acknowledgements

We wish to thank the participants and their families. The work was supported by the Hôpitaux Universitaires de Genève (Geneva, Switzerland) and the Association pour l'Etude du Sommeil (Montpellier, France).

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Authors and Affiliations

  1. Neurologie B, Hôpital Gui-de-Chauliac, Montpellier-France, France

    Y Dauvilliers & M Billiard

  2. Département de Psychiatrie, Unité de Biochimie et Génétique, Université de Genève-Suisse, France

    Y Dauvilliers, E Neidhart & M Tafti

  3. Hôpital Robert Debré, Paris, France

    M Lecendreux

Authors
  1. Y Dauvilliers
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  2. E Neidhart
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  3. M Lecendreux
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  4. M Billiard
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  5. M Tafti
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Corresponding author

Correspondence to M Tafti.

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Dauvilliers, Y., Neidhart, E., Lecendreux, M. et al. MAO-A and COMT polymorphisms and gene effects in narcolepsy. Mol Psychiatry 6, 367–372 (2001). https://doi.org/10.1038/sj.mp.4000911

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