Association between the functional variant of the catechol-O-methyltransferase (COMT) gene and type 1 alcoholism (original) (raw)

Molecular Psychiatry volume 4, pages 286–289 (1999)Cite this article

Abstract

Catechol-O-methyltransferase (COMT) is an enzyme which has a crucial role in the metabolism of dopamine. It has been suggested that a common functional genetic polymorphism in the COMT gene, which results in 3 to 4-fold difference in COMT enzyme activity,1,2 may contribute to the etiology of mental disorders such as bipolar disorder and alcoholism.1 Since ethanol-induced euphoria is associated with the rapid release of dopamine in limbic areas, it is conceivable that subjects who inherit the allele encoding the low activity COMT variant would have a relatively low dopamine inactivation rate, and therefore would be more vulnerable to the development of ethanol dependence. The aim of this study was to test this hypothesis among type 1 (late-onset) alcoholics. The COMT polymorphism was determined in two independent male late onset (type 1) alcoholic populations in Turku (n = 67) and Kuopio (n = 56). The high (H) and low (L) activity COMT genotype and allele frequencies were compared with previously published data from 3140 Finnish blood donors (general population) and 267 race- and gender-matched controls. The frequency of low activity allele (L) was markedly higher among the patients both in Turku (P = 0.023) and in Kuopio (P = 0.005) when compared with the general population. When all patients were compared with the general population (blood donors), the difference was even more significant (P = 0.0004). When genotypes of all alcoholics (n = 123) were compared with genotypes of matched controls, the odds ratio (OR) for alcoholism for those subjects having the LL genotype vs those with HH genotype was 2.51, 95% CI 1.22–5.19, P = 0.006. Also, L allele frequency was significantly higher among alcoholics when compared with controls (P = 0.009). The estimate for population etiological (attributable) fraction for the LL genotype in alcoholism was 13.3% (95% CI 2.3–25.7%). The results indicate that the COMT polymorphism contributes significantly to the development of late-onset alcoholism.

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Authors and Affiliations

  1. Department of Forensic Psychiatry, University of Kuopio, Niuvanniemi Hospital, Kuopio, Finland
    J Tiihonen & T Hallikainen
  2. Department of Clinical Physiology, Kuopio University Hospital, Kuopio, Finland
    J Tiihonen
  3. Albert Einstein College of Medicine, New York, USA
    H Lachman & T Saito
  4. Nathan Kline Institute, Orangeburg, New York, USA
    J Volavka
  5. Department of Public Health and General Practice, University of Kuopio, Kuopio, Finland
    J Kauhanen, J T Salonen & O-P Ryynänen
  6. Research Institute of Public Health, University of Kuopio, Kuopio, Finland
    J Kauhanen & J T Salonen
  7. Department of Pharmacology, University of Turku, Turku, Finland
    M Koulu, M K Karvonen, T Pohjalainen & E Syvälahti
  8. Department of Psychiatry, Turku University Central Hospital, Turku, Finland
    J Hietala

Authors

  1. J Tiihonen
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  2. T Hallikainen
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  3. H Lachman
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  4. T Saito
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  5. J Volavka
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  6. J Kauhanen
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  7. J T Salonen
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  8. O-P Ryynänen
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  9. M Koulu
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  10. M K Karvonen
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  11. T Pohjalainen
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  12. E Syvälahti
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  13. J Hietala
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Corresponding author

Correspondence toJ Tiihonen.

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Tiihonen, J., Hallikainen, T., Lachman, H. et al. Association between the functional variant of the catechol-O-methyltransferase (COMT) gene and type 1 alcoholism.Mol Psychiatry 4, 286–289 (1999). https://doi.org/10.1038/sj.mp.4000509

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