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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. [ABSTRACT FROM AUTHOR]