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

✍ Scribed by Vandenbergh, David J.; Rodriguez, Lawrence A.; Miller, Ivan T.; Uhl, George R.; Lachman, Herbert M.

• Publisher: John Wiley and Sons
• Year: 1997
• Tongue: English
• Weight: 12 KB
• Volume: 74
• Category: Article
• ISSN: 0148-7299
• DOI: 10.1002/(sici)1096-8628(19970725)74:4<439::aid-ajmg16>3.0.co;2-j

✦ Synopsis

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 fourfold. 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.