High-activity catechol-O-methyltransferase allele is more prevalent in polysubstance abusers.
Allelic variants at the catechol-O-methyltransferase (COMT) locus are candidates to contribute to genetic components of interindividual differences in vulnerability to substance abuse. COMT plays a prominent role in dopaminergic circuits important for drug reward, and COMT alleles encode enzymes whose activities vary from three- to four-fold. We compared COMT allele frequencies in control research volunteers reporting insignificant lifetime use of addictive substances with those in volunteers reporting substantial polysubstance use. Homozygosity for the high-activity COMT allele was found in 18% of controls, 31% of volunteers with high lifetime substance use, and 39% meeting DSMIII-R substance abuse criteria [odds ratio (relative risks) 2.0 (control vs. use; 95% confidence interval 1.2-3.5; P < 0.013) and 2.8 (control vs. DSM; 1.3-6.1; P < 0.008)]. Individuals with the high-activity COMT variant may have greater genetic vulnerability to drug abuse.
Vandenbergh
D J
DJ
Molecular Neurobiology Branch, Intramural Research Program, National Institute on Drug Abuse, NIH, Baltimore, Maryland, USA.
Rodriguez
L A
LA
Miller
I T
IT
Uhl
G R
GR
Lachman
H M
HM
D000483:Alleles; D002394:Catechol O-Methyltransferase / Q000235:genetics*; D003062:Codon / Q000235:genetics; D004198:Disease Susceptibility; D004298:Dopamine / Q000378:metabolism; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D016017:Odds Ratio; D012150:Polymorphism, Restriction Fragment Length; D012201:Reward; D019966:Substance-Related Disorders / Q000235:genetics*
D003062:Codon; D002394:Catechol O-Methyltransferase; D004298:Dopamine