Lawford B R, Young R M, Noble E P, Sargent J, Rowell J, Shadforth S, Zhang X, Ritchie T
Department of Psychiatry, The University of Queensland, Brisbane, Australia.
Am J Med Genet. 2000 Oct 9;96(5):592-8. doi: 10.1002/1096-8628(20001009)96:5<592::aid-ajmg3>3.0.co;2-y.
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.
在一项门诊美沙酮治疗项目中，对95名白种人阿片类药物依赖患者进行了为期一年的跟踪研究。这些患者中，D2多巴胺受体（DRD2）基因的TaqI A(1)等位基因频率为19.0%，而在无既往及当前酒精和其他药物滥用且无酒精和其他药物滥用家族史的对照组中，该频率为4.6%（p = 0.009）。这些患者中有22人退出了美沙酮项目（A组），54人治疗成功（B组），19人治疗效果不佳（C组）。A(1)等位基因频率在C组最高（42.1%），其次是A组（22.7%），在B组最低（9.3%）。治疗效果不佳组的A(1)等位基因频率比治疗成功组高出四倍多，差异具有统计学意义（p = 0.00002）。此外，在研究入组前一年，携带A(1)(+)等位基因（A(1)/A(1)或A(1)/A(2)基因型）的患者海洛因平均使用量（克/天）是携带A(1)(-)等位基因（A(2)/A(2)基因型）患者的两倍多（A(1)(+)等位基因 = 0.55 ± 0.10，A(1)(-)等位基因 = 0.25 ± 0.05；p = 0.003）。结果表明，DRD2变异体是海洛因使用及后续美沙酮治疗效果的预测指标，并提示了一种针对阿片类药物依赖治疗的药物遗传学方法。
