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 pathways of neurotransmitters such as dopamine, adrenaline, and noradrenaline. The activity of COMT is known to vary within the population; it exists in 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 COMT). Recently, the low-activity allele was reported to contribute to the development of late-onset alcoholism in men. The present study extends this study by utilizing a family-based association approach, and by including individuals with early-onset alcoholism. Although no significant transmission disequilibrium was found in the overall sample of 70 parent/offspring trios (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, TDT = 4.83, P = 0.028). Our results provide further evidence for an involvement of the COMT low-activity allele in the development of alcoholism and demonstrate the need for further studies in large samples of alcoholic patients.
Wang
T
T
Institute of Human Genetics, University of Bonn, Wilhelmstr 31, 53111 Bonn, Germany.
Franke
P
P
Neidt
H
H
Cichon
S
S
Knapp
M
M
Lichtermann
D
D
Maier
W
W
Propping
P
P
Nöthen
M M
MM
D000328:Adult; D017668:Age of Onset; D000437:Alcoholism / Q000235:genetics*; D000483:Alleles; D001921:Brain / Q000201:enzymology; D002394:Catechol O-Methyltransferase / Q000235:genetics*; D005192:Family Health; D005260:Female; D006801:Humans; D008297:Male; D020641:Polymorphism, Single Nucleotide
D002394:Catechol O-Methyltransferase