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Cited by 189Neurotransmitter Receptor Influence on BehaviorGenetic Associations and EpidemiologySubstance Abuse Treatment and Outcomes

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

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·Molecular Psychiatry
DOI 10.1038/sj.mp.4000509
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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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Metadata

Authors
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.
Affiliations
  • Niuvanniemi Hospital (FI)
  • Albert Einstein College of Medicine (US)
  • Nathan Kline Institute for Psychiatric Research (US)
  • University of Eastern Finland (FI)
  • University of Turku (FI)
  • Turku University Hospital (FI)
Corresponding author
Tiihonen, J
ORCID
Venue
Molecular Psychiatry
Publisher
Springer Science and Business Media LLC
Published
1999-05-01
Volume
4
Issue
3
Pages
286-289
ISSN
  • 1359-4184 (ISSN-L)
  • 1476-5578
DOI
10.1038/sj.mp.4000509
OpenAlex
W2034763673
Cited by
189
References
0
Citations by year
2025: 1 · 2024: 2 · 2023: 1 · 2022: 4 · 2021: 4 · 2020: 1 · 2019: 5 · 2018: 2 · 2017: 7 · 2016: 3 · 2015: 9 · 2014: 6 · 2013: 3 · 2012: 13
FWCI
2.66
Type
journal article
Language
en
Open access
closed
Licence
Locations
  • Molecular Psychiatry (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
  • Health Sciences › Medicine › Epidemiology › Substance Abuse Treatment and Outcomes
Keywords
catechol-O-methyltransferase, COMT gene, genetic polymorphism, late-onset alcoholism, alcoholism, dopamine metabolism, genetic susceptibility, Finnish population
MeSH terms
Adult, Alcoholism, Alleles, Catechol O-Methyltransferase, Finland, Gene Frequency, Genotype, Humans, Male, Middle Aged, Risk Factors, Genetic Variation, Myocardial Ischemia

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