ANKK1 and DRD2 pharmacogenetics of disulfiram treatment for cocaine abuse

作者：Spellicy Catherine J^*; Kosten Thomas R; Hamon Sara C; Harding Mark J; Nielsen David A

来源：Pharmacogenetics and Genomics, 2013, 23(7): 333-340.

DOI：10.1097/FPC.0b013e328361c39d

• ankyrin repeat and kinase domain-containing 1
• cocaine
• dependence
• disulfiram
• dopamine receptor D2
• treatment

ObjectiveDisulfiram is a potential cocaine addiction pharmacotherapy. Since dopamine deficiency has been found with cocaine addiction, our objective was to examine whether functional variants in the ankyrin repeat and kinase domain-containing 1 (ANKK1) and/or the dopamine receptor D2 (DRD2) genes interact with response to treatment with disulfiram.Materials and methodsCocaine and opioid codependent (DSM-IV) patients were stabilized on methadone and subsequently randomized into treatment groups - disulfiram (250 mg/day, N=31) or placebo (N=37). They were genotyped for ANKK1 (rs1800497) and DRD2 (rs2283265) polymorphisms, and the data were evaluated for an association between a cocaine-free state, as assessed by cocaine-free urine samples, and disulfiram treatment. Data were analyzed using repeated measures analysis of variance corrected for population structure.ResultsPatients with CT or TT ANKK1 genotypes dropped from 80 to 52% cocaine-positive urines on disulfiram (N=13; P0.0001), whereas those on placebo (N=20) showed no treatment effect. Patients carrying the CC ANKK1 genotype showed no effect on treatment with disulfiram (N=18) or placebo (N=17). The GT/TT DRD2 genotype group showed a significant decrease in the number of cocaine-positive urine samples on disulfiram (N=9; 67-48%; P0.0001), whereas the GG DRD2 genotype group showed only a marginal decrease (N=23; 84-63%; P=0.04). Genotype pattern analysis revealed that individuals carrying at least one minor allele in either gene responded better to disulfiram treatment (N=13; P0.0001) compared with individuals carrying only the major alleles (N=17).ConclusionA patient%26apos;s genotype for ANKK1, DRD2, or both, may be used to identify individuals for whom disulfiram may be an effective pharmacotherapy for cocaine dependence.

• 出版日期2013-7