Association study of the low-activity allele of catechol-O-methyltransferase and alcoholism using a family-based approach

Catechol-O-methyltransferase (COMT) is a major component of the metabolic p athways of neurotransmitters such as dopamine, adrenaline, and noradrenalin e. The activity of COMT is known to vary within the population; it exists i n common high- and low-activity forms that are determined by a Val --> Met polymorphism at amino acid position 108/158 (in soluble or membrane-bound C OMT). Recently, the low-activity allele was reported to contribute to the d evelopment of late-onset alcoholism in men.(1) The present study extends th is study by utilizing a family-based association approach, and by including individuals with early-onset alcoholism. Although no significant transmiss ion disequilibrium was found in the overall sample of 70 parent/offspring t rios (TDT = 1.43, P = 0.23), we observed a preferential transmission of the low-activity allele to patients with an early onset of disease (n = 32, TD T = 4.83, P = 0.028). Our results provide further evidence for an involveme nt of the COMT low-activity allele in the development of alcoholism and dem onstrate the need for further studies in large samples of alcoholic patient s.