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

J. Tiihonen, T. Hallikainen, H. Lachman, T. Saito, J. Volavka, J. Kauhanen, J. T. Salonen, O. P. Ryynänen, M. Koulu, M. K. Karvonen, T. Pohjalainen, E. Syvälahti, J. Hietala

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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, may contribute to the etiology of mental disorders such as bipolar disorder and alcoholism. 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.

Original languageEnglish (US)
Pages (from-to)286-289
Number of pages4
JournalMolecular Psychiatry
Issue number3
StatePublished - 1999


  • Alcoholism
  • COMT
  • Catechol-O-methyltransferase
  • Dopamine
  • Polymorphism
  • Substance-abuse disorders

ASJC Scopus subject areas

  • Molecular Biology
  • Psychiatry and Mental health
  • Cellular and Molecular Neuroscience

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    Tiihonen, J., Hallikainen, T., Lachman, H., Saito, T., Volavka, J., Kauhanen, J., Salonen, J. T., Ryynänen, O. P., Koulu, M., Karvonen, M. K., Pohjalainen, T., Syvälahti, E., & Hietala, J. (1999). Association between the functional variant of the catechol-O-methyltransferase (COMT) gene and type 1 alcoholism. Molecular Psychiatry, 4(3), 286-289.