Nine- or fewer repeat alleles in VNTR polymorphism of the dopamine transporter gene is a strong risk factor for prolonged methamphetamine psychosis

Abstract

Susceptibility to drug dependence and drug-induced psychoses is influenced not only by the pharmacological effects of the drug but also by the genetic factors of the individual. To clarify the latter, we investigated the association between methamphetamine (METH) dependence/psychosis and the hDAT1 gene (SLC6A3) encoding the dopamine transporter, which is the primary site of METH activity in the brain. Four exonic polymorphisms of the hDAT1 gene, 242C/T (exon 2), 1342A/G (exon 9), 2319G/A (3 0 UTR), and VNTR (3 0 UTR) were examined. Although there was no significant difference in genotypic and allelic distribution of the four polymorphisms between all METH dependence/psychosis patients (N ¼ 124) and controls (N ¼ 160), the patients with METH psychosis lasting for 1 month or more after discontinuance of METH consumption showed a significant excess of nine-or fewer repeat alleles of the VNTR in 3 0 UTR of the hDAT1 gene (P ¼ 0.0054, OR ¼ 4.24, 95% CI ¼ 2. 46-7.31). The present study demonstrated that the presence of nineor fewer repeat alleles of hDAT1 is a strong risk factor for a worse prognosis of METH psychosis.

Behavioral genetic contributions to the study of addiction-related amphetamine effects

“…Some data support an association of number of repeat alleles of the DAT gene with risk for methamphetamine psychosis (Ujike et al, 2003). Further, DAT density, quantified using positron emission tomography, was decreased in methamphetamine users compared to non-users .…”

Dopamine Transporter Genotype and Methylphenidate Dose Response in Children with ADHD

“…Thus, when the 9/9 is not combined with the 9/10 genotype, there appears to be a clear difference in stimulant response. In addition, there are also studies reporting atypical stimulant response in individuals with the 9-repeat allele in other patient groups (see Gelernter et al, 1994;Ujike et al, 2003).…”

Linkage disequilibrium and association with methamphetamine dependence/psychosis of μ-opioid receptor gene polymorphisms

“…32,33 The median latency was 3 years. Therefore, patients were divided into two categories based on the latency of the psychotic state after the first MAP intake: less than 3 years (n ¼ 54, average ¼ 0.83 years) or more than 3 years (n ¼ 53, average ¼ 9.98 years).…”

“…(b) Duration of psychosis after the last MAP intake: Some patients showed continued psychotic symptoms despite MAP abstinence, as reported previously. 32,33 Liability for the duration of psychosis may be determined, at least partly, by genetic variation. We previously reported that genetic variation in the dopamine transporter affects the prognosis of the psychotic state.…”