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.
Institute of Human Genetics, University of Bonn, Wilhelmstr 31, 53111 Bonn, Germany.
T
T
Wang
P
P
Franke
H
H
Neidt
S
S
Cichon
M
M
Knapp
D
D
Lichtermann
W
W
Maier
P
P
Propping
M M
MM
Nöthen
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