The D(2) dopamine receptor A(1) allele and opioid dependence: association with heroin use and response to methadone treatment.
A total of 95 Caucasian opioid-dependent patients were followed over a one-year period in an outpatient methadone treatment program. The frequency of the TaqI A(1) allele of the D(2) dopamine receptor (DRD2) gene was 19.0% in these patients compared with 4.6% in controls free of past and current alcohol and other drug abuse and free of family history of alcohol and other drug abuse (p = 0.009). Twenty-two of these patients dropped out of the methadone program (Group A), 54 had a successful treatment (Group B), and 19 had a poor treatment (Group C) outcome. The frequency of the A(1) allele was highest in Group C (42.1%), followed by Group A (22.7%) and was lowest in Group B (9.3%). The more than fourfold higher frequency of the A(1) allele in the poor treatment outcome group compared with the successful treatment outcome group was significant (p = 0.00002). Moreover, the average use of heroin (grams/day) during the year prior to study entry was more than twice as great in patients with the A(1)(+) allele (A(1)/A(1) or A(1)/A(2) genotype) than those with the A(1)(-) allele (A(2)/A(2) genotype) (A(1)(+) allele = 0.55 +/- 0. 10, A(1)(-) allele = 0.25 +/- 0.05; p = 0.003). The results indicate that DRD2 variants are predictors of heroin use and subsequent methadone treatment outcome and suggest a pharmacogenetic approach to the treatment of opioid dependence.
Lawford
B R
BR
Department of Psychiatry, The University of Queensland, Brisbane, Australia.
Young
R M
RM
Noble
E P
EP
Sargent
J
J
Rowell
J
J
Shadforth
S
S
Zhang
X
X
Ritchie
T
T
D000328:Adult; D000483:Alleles; D000701:Analgesics, Opioid / Q000627:therapeutic use; D000704:Analysis of Variance; D004247:DNA / Q000235:genetics; D005260:Female; D005500:Follow-Up Studies; D005787:Gene Frequency; D005838:Genotype; D003932:Heroin / Q000008:administration & dosage; D006801:Humans; D008297:Male; D008691:Methadone / Q000627:therapeutic use; D009293:Opioid-Related Disorders / Q000235:genetics* / Q000534:rehabilitation; D017448:Receptors, Dopamine D2 / Q000235:genetics*
D000701:Analgesics, Opioid; D017448:Receptors, Dopamine D2; D003932:Heroin; D004247:DNA; D008691:Methadone