Long forms of the dopamine receptor (DRD4) gene VNTR are more prevalent insubstance abusers: No interaction with functional alleles of the catechol-o-methyltransferase (COMT) gene

Substance abuse is a complex behavior that is caused by both environmental and genetic factors. Work to understand the genetic factors has focused on genes related to dopamine activity because of its critical role in rewardin g and reinforcing behaviors, The DRD3 and other dopamine receptor subtypes are expressed in many areas of the limbic system, and have been the objects of study for their possible roles in several neuropsychiatric disorders. I nterest in variants of the D4 gene was heightened by reports that some alle les were more frequent in individuals who score high on Novelty Seeking, an aspect of personality that may be related to drug seeking behavior, We now show that the long form of the DRD4 gene is more frequent in individuals w ith high quantity/frequency of drug use compared to controls (chi(2) = 5.7, df = 1, P = 0.017, odds ratio = 1.89, CI = 1.1-3.2), There is no differenc e in DRD3 allele frequencies in these samples, and there is no interaction of DRD4 alleles with those of the catecholamine-o-methyltransferase gene (C OMT) that we previously identified to be more frequent in substance abusers than controls [Vandenbergh, et al,: 1997: Am. J. Med. Gen. 74:439-442]. Am . J, Med, Genet, (Neuropsychiatr. Genet.) 96: 678-683, 2000, Published 2000 Wiley-Liss, Inc.(dagger).