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

J. Tiihonen, T. Hallikainen, Herbert M. 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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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, 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
Volume4
Issue number3
StatePublished - 1999

Fingerprint

Catechol O-Methyltransferase
Alcoholism
Genotype
Genes
Alcoholics
Dopamine
Population
Blood Donors
Gene Frequency
Ethanol
Alleles
Genetic Polymorphisms
Enzymes
Bipolar Disorder
Mental Disorders
Odds Ratio

Keywords

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

ASJC Scopus subject areas

  • Molecular Biology
  • Psychiatry and Mental health

Cite this

Tiihonen, J., Hallikainen, T., Lachman, H. M., Saito, T., Volavka, J., Kauhanen, J., ... 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.

Association between the functional variant of the catechol-O-methyltransferase (COMT) gene and type 1 alcoholism. / Tiihonen, J.; Hallikainen, T.; Lachman, Herbert M.; Saito, T.; Volavka, J.; Kauhanen, J.; Salonen, J. T.; Ryynänen, O. P.; Koulu, M.; Karvonen, M. K.; Pohjalainen, T.; Syvälahti, E.; Hietala, J.

In: Molecular Psychiatry, Vol. 4, No. 3, 1999, p. 286-289.

Research output: Contribution to journalArticle

Tiihonen, J, Hallikainen, T, Lachman, HM, Saito, T, Volavka, J, Kauhanen, J, Salonen, JT, Ryynänen, OP, Koulu, M, Karvonen, MK, 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, vol. 4, no. 3, pp. 286-289.
Tiihonen, J. ; Hallikainen, T. ; Lachman, Herbert M. ; Saito, T. ; Volavka, J. ; Kauhanen, J. ; Salonen, J. T. ; Ryynänen, O. P. ; Koulu, M. ; Karvonen, M. K. ; Pohjalainen, T. ; Syvälahti, E. ; Hietala, J. / Association between the functional variant of the catechol-O-methyltransferase (COMT) gene and type 1 alcoholism. In: Molecular Psychiatry. 1999 ; Vol. 4, No. 3. pp. 286-289.
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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, 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.",
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