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 i n the metabolism of dopamine. It has been suggested that a common functiona l genetic polymorphism in the COMT gene, which results in 3 to 4-fold diffe rence in COMT enzyme activity,(1,2) may contribute to the etiology of menta l disorders such as bipolar disorder and alcoholism.(1) Since ethanol-induc ed euphoria is associated with the rapid release of dopamine in limbic area s, it is conceivable that subjects who inherit the allele encoding the low activity COMT variant would have a relatively low dopamine inactivation rat e, and therefore would be more vulnerable to the development of ethanol dep endence. The aim of this study was to test this hypothesis among type 1 (la te-onset) alcoholics. The COMT polymorphism was determined in two independe nt male late onset (type 1) alcoholic populations in Turku (n = 67) and Kuo pio (n = 56). The high (H) and low (L) activity COMT genotype and allele fr equencies were compared with previously published data from 3140 Finnish bl ood donors (general population) and 267 race- and gender-matched controls. The frequency of low activity allele (L) was markedly higher among the pati ents 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 p opulation (blood donors), the difference was even more significant (P = 0.0 004). When genotypes of all alcoholics (n = 123) were compared with genotyp es of matched controls, the odds ratio (OR) for alcoholism for those subjec ts 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 alc oholics when compared with controls (P = 0.009). The estimate for populatio n 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.