The D-2 dopamine receptor al 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 TaqIA(1) allele of the D-2 dopamine receptor (DRD2) gene was 19.0% in t hese patients compared with 4.6% in controls free of past and current alcoh ol and other drug abuse and free of family history of alcohol and other dru g abuse (p = 0.009). Twenty-two of these patients dropped out of the methad one 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 hi ghest in Group C (42.1%), followed by Group A (22.7%) and was lowest in Gro up 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 out come group was significant (p = 0.00002). Moreover, the average use of hero in (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 indi cate that DRD2 variants are predictors of heroin use and subsequent methado ne treatment outcome and suggest a pharmacogenetic approach to the treatmen t of opioid dependence. Am. J. Med. Genet. (Neuropsychiatr. Genet.) 96:592- 598, 2000. (C) 2000 Wiley-Liss, Inc.