Vandenbergh D J, Rodriguez L A, Miller I T, Uhl G R, Lachman H M
Molecular Neurobiology Branch, Intramural Research Program, National Institute on Drug Abuse, NIH, Baltimore, Maryland, USA.
Am J Med Genet. 1997 Jul 25;74(4):439-42.
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.
儿茶酚-O-甲基转移酶（COMT）基因座的等位基因变异可能是导致个体对药物滥用易感性差异的遗传因素之一。COMT在对药物奖赏至关重要的多巴胺能回路中起着重要作用，且COMT等位基因编码的酶活性相差三到四倍。我们比较了报告终生使用成瘾物质不显著的对照研究志愿者与报告大量使用多种物质的志愿者的COMT等位基因频率。在18%的对照者、31%终生大量使用物质的志愿者以及39%符合DSM-III-R药物滥用标准的志愿者中发现了高活性COMT等位基因的纯合性[优势比（相对风险）分别为2.0（对照者与使用者相比；95%置信区间1.2 - 3.5；P < 0.013）和2.8（对照者与符合DSM标准者相比；1.3 - 6.1；P < 0.
