Polymorphisms of the DRD2 , ANKK1 , DAT1 , DBH , and DRD4 genes have been found to moderate the effects of pharmacotherapy  of alcohol , opioid , and cocaine use disorders .
The integration of genetic information with clinical data will inform health professionals of the most efficacious pharmacotherapeutic intervention for substance use disorders .
Substance use disorders have significant personal , familial , and societal consequences .
Despite the serious consequences of substance use , only a few therapies are effective in treating substance use disorders , thus highlighting a need for improved treatment practice s. Substance use treatment response depends on multiple factors such as genetic , biological , and social factors .
It is essential that each component is represented in treatment plans .
The dopaminergic system plays a critical role in the pharmacotherapy for addictions , and an underst and ing of the role of variation of genes involved in this system is essential for its success .
ANKK1 and DRD2 pharmacogenetics of disulfiram treatment for cocaine abuse
Objective Disulfiram 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 . Material s and methods Cocaine and opioid codependent ( DSM-IV ) patients were stabilized on methadone and subsequently r and omized 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 sample s , and disulfiram treatment . Data were analyzed using repeated measures analysis of variance corrected for population structure . Results Patients with CT or TT ANKK1 genotypes dropped from 80 to 52 % cocaine-positive urines on disulfiram ( N=13 ; P⩽0.0001 ) , 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 sample s on disulfiram ( N=9 ; 67–48 % ; P⩽0.0001 ) , 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 ; P⩽0.0001 ) compared with individuals carrying only the major alleles ( N=17 ) . Conclusion A patient ’s genotype for ANKK1 , DRD2 , or both , may be used to identify individuals for whom disulfiram may be an effective pharmacotherapy for cocaine dependence
Polymorphisms of the DRD2 , ANKK1 , DAT1 , DBH , and DRD4 genes have been found to moderate the effects of pharmacotherapy  of alcohol , opioid , and cocaine use disorders .
The integration of genetic information with clinical data will inform health professionals of the most efficacious pharmacotherapeutic intervention for substance use disorders .
Substance use disorders have significant personal , familial , and societal consequences .
Despite the serious consequences of substance use , only a few therapies are effective in treating substance use disorders , thus highlighting a need for improved treatment practice s. Substance use treatment response depends on multiple factors such as genetic , biological , and social factors .
It is essential that each component is represented in treatment plans .
The dopaminergic system plays a critical role in the pharmacotherapy for addictions , and an underst and ing of the role of variation of genes involved in this system is essential for its success .