Center for Neurobiology and Behavior, Department of Psychiatry, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA.
Clinical Pharmacology and Therapeutics Research Branch, Intramural Research Program, National Institute on Drug Abuse, Baltimore, MD, USA.
Pharmacogenomics J. 2019 Jun;19(3):260-268. doi: 10.1038/s41397-018-0065-x. Epub 2018 Oct 27.
Many patients with opioid use disorder do not have successful outcomes during treatment but the underlying reasons are not well understood. An OPRD1 variant (rs678849) was previously associated with methadone and buprenorphine efficacy in African-Americans with opioid use disorder. The objective of this study was to determine if the effect of rs678849 on opioid use disorder treatment outcome could be replicated in an independent population. Participants were recruited from African-American patients who had participated in previous studies of methadone or buprenorphine treatment at the outpatient treatment research clinic of the NIDA Intramural Research Program in Baltimore, MD, USA between 2000 and 2017. Rs678849 was genotyped retrospectively, and genotypes were compared with urine drug screen results from the previous studies for opioids other than the one prescribed for treatment. Genotypes were available for 24 methadone patients and 55 buprenorphine patients. After controlling for demographics, the effect of rs678849 genotype was significant in the buprenorphine treatment group (RR = 1.69, 95% confidence interval (CI) 1.59-1.79, p = 0.021). Buprenorphine patients with the C/C genotype were more likely to have opioid-positive drug screens than individuals with the C/T or T/T genotypes, replicating the original pharmacogenetic finding. The effect of genotype was not significant in the methadone group (p = 0.087). Thus, the genotype at rs678849 is associated with buprenorphine efficacy in African-Americans being treated for opioid use disorder. This replication suggests that rs678849 genotype may be a valuable pharmacogenetic marker for deciding which opioid use disorder medication to prescribe in this population.
许多患有阿片类药物使用障碍的患者在治疗过程中没有取得成功，但其中的原因尚不清楚。先前的研究表明，OPRD1 变体(rs678849)与阿片类药物使用障碍的非洲裔美国人中美沙酮和丁丙诺啡的疗效有关。本研究的目的是确定 rs678849 对阿片类药物使用障碍治疗结果的影响是否可以在一个独立的人群中得到复制。参与者是从美国马里兰州巴尔的摩 NIDA 院内研究计划的门诊治疗研究诊所参加过去美沙酮或丁丙诺啡治疗研究的非洲裔美国人患者中招募的。rs678849 是通过回顾性基因分型来确定的，并将其与之前研究中除了用于治疗的药物之外的其他阿片类药物的尿液药物检测结果进行比较。rs678849 基因型可用于 24 名美沙酮患者和 55 名丁丙诺啡患者。在控制人口统计学因素后，rs678849 基因型在丁丙诺啡治疗组中的作用显著(RR=1.69，95%置信区间(CI)1.59-1.79，p=0.021)。C/C 基因型的丁丙诺啡患者比 C/T 或 T/T 基因型的患者更有可能出现阿片类药物阳性药物检测结果，复制了最初的药物遗传学发现。基因型在美沙酮组中的作用不显著(p=0.087)。因此，rs678849 基因型与接受阿片类药物使用障碍治疗的非洲裔美国人丁丙诺啡的疗效有关。这种复制表明，rs678849 基因型可能是决定在该人群中开哪种阿片类药物使用障碍药物的有价值的药物遗传学标志物。
