DRD4 exon IIIVNTR polymorphism-susceptibility factor for heroin dependence? Results of a case-control and a family-based association approach

Dopaminergic abnormalities are implicated in the pathogenesis of substance abuse.(1) Recently, two reports have been published suggesting an association between opioid dependence and presence of long alleles of the dopamine D-4 receptor (DRD4) gene exon III VNTR.(2,3) We have attempted to replicate this finding using a two-tiered strategy employing independent case-control and family-based association samples. Our study was possibly the largest candidate gene association study to date on opioid dependence in a sample of 815 subjects, 396 of whom were patients. We found long alleles of the DRD4 exon III VNTR in similar frequency among 285 heroin addicts and 197 controls. Furthermore, no preferential transmission of long alleles to affected offspring was observed in a sample of 111 patients and their parents. Our results, therefore, do not support the hypothesis that alleles of the DRD4 exon III VNTR are susceptibility factors for opioid dependence in man.