High-activity catechol-O-methyltransferase allele is more prevalent in polysubstance abusers

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169 Scopus citations


Allelic variants at the catechol-O-methyl-transferase (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.

Original languageEnglish (US)
Pages (from-to)439-442
Number of pages4
JournalAmerican Journal of Medical Genetics - Neuropsychiatric Genetics
Issue number4
StatePublished - Sep 1 1997


  • Abuse
  • Cocaine
  • Dopamine
  • Opiates
  • Polymorphism

ASJC Scopus subject areas

  • Genetics(clinical)
  • Psychiatry and Mental health
  • Cellular and Molecular Neuroscience


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