Association between the functional variant of the catechol-O-methyltransferase (COMT) gene and type 1 alcoholism.
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.
Department of Forensic Psychiatry, University of Kuopio, Niuvanniemi Hospital, Finland. Jari.Tiihonen@niuva.fi
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J
Tiihonen
T
T
Hallikainen
H
H
Lachman
T
T
Saito
J
J
Volavka
J
J
Kauhanen
J T
JT
Salonen
O P
OP
Ryynänen
M
M
Koulu
M K
MK
Karvonen
T
T
Pohjalainen
E
E
Syvälahti
J
J
Hietala
D000328:Adult; D000437:Alcoholism / Q000201:enzymology / Q000235:genetics* / Q000523:psychology; D000483:Alleles; D002394:Catechol O-Methyltransferase / Q000235:genetics* / Q000378:metabolism; D005387:Finland / Q000453:epidemiology; D005787:Gene Frequency; D014644:Genetic Variation; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D017202:Myocardial Ischemia / Q000453:epidemiology / Q000235:genetics; D012307:Risk Factors
D002394:Catechol O-Methyltransferase