Association analysis of dopamine D2-like receptor genes and methamphetamine abuse

Objectives Substance use disorders are familial, and genetic factors explain a substantial degree of their familial aggregation. This study employs an association approach to examine the genetic underpinning of methamphetamine (MAMP) use and MAMP-induced psychosis. Methods A total of 416 MAMP abusers from a hospital and a detention center in Taipei were interviewed with the Diagnostic Interview for Genetic Study and the Family Interview for Genetic Study. Genetic polymorphisms of D2-like dopamine receptor genes, DRD2 TaqI A, DRD3 Ser-9-Gly, and DRD4 exon III variable number of tandem repeats, were compared between: (a) MAMP users as a whole and 435 normal controls, and (b) those 154 individuals with MAMP-induced psychosis and the 252 MAMP users with no psychosis. Results None of the three markers we studied were associated with predisposition to psychosis among the MAMP abusers. The MAMP abusers had a higher (P=0.011) prevalence of the seven-repeat allele of DRD4 than normal controls. Conclusions Chance fluctuations in the frequency of rare alleles and ascertainment differences in the case and control samples cannot be ruled out. Therefore, further studies of the seven-repeat allele in MAMP abusers and controls should be performed before an association can be established.