Replication of the pharmacogenetic effect of rs678849 on buprenorphine efficacy in African–Americans with opioid use disorder

Abstract

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 to 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, 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.

A Delta-Opioid Receptor Gene Polymorphism Moderates the Therapeutic Response to Extended-Release Buprenorphine in Opioid Use Disorder

“…The missing data analyses showed genotype by medication effects with the same direction and magnitude as those in the primary analyses. Thus, although we did not replicate the findings of Crist et al (2013 , 2019 ) of a moderating effect of rs678849 on the response to buprenorphine in AAs, we found such an effect in EAs, which Crist et al (2013) did not.…”

“…The study showed no moderating effect of the SNP in the 566 European-American (EA) participants ( Crist et al, 2013 ). In an independent sample of 55 AA buprenorphine-treated patients ( Crist et al, 2019 ), the risk ratio for opioid-positive UDS associated with the CC genotype was 1.69, thereby replicating the initial finding that Crist et al (2013) obtained in AAs, but not EAs. Combining data across the 2 studies, buprenorphine-treated AA patients with the CC genotype had opioid-positive UDS 56.3% of the time, compared with 30.7% for patients in the combined CT and TT genotype groups ( P < .0001).…”

“…Differentiating patients unlikely to respond well to buprenorphine treatment could potentially prevent a delay in their being treated with methadone or long-acting naltrexone, 2 other medications approved for treating OUD. In 2 retrospective analyses of sublingual buprenorphine (BUP-SL), an intronic single nucleotide polymorphism (SNP), rs678849 in OPRD1 , which encodes the delta-opioid receptor, moderated the response to buprenorphine treatment of OUD in African Americans (AAs) ( Crist et al, 2013 , 2019 ). In the first study, a 24-week comparison of buprenorphine vs methadone in 77 AAs, of the 41 buprenorphine-treated patients, those with the rs678849*CT or TT genotype (n = 17 with either CT or TT) had significantly fewer opioid-positive urine drug screens (UDS) (30.7% ± 32.3) than those with the CC genotype (n = 24; 60.7% ± 37.2; P < .004).…”

Molecular Imaging of Opioid and Dopamine Systems: Insights Into the Pharmacogenetics of Opioid Use Disorders

“…In addition, several studies have investigated the effects of OPRD1 polymorphisms on treatment outcomes in OUD. For example, the major allele of rs678849 has been associated with higher relapse rates among African American OUD patients undergoing buprenorphine treatment, as indicated by positive opioid urine tests (148, 149). Interestingly, the major allele was initially associated with lower relapse rates among African American OUD patients on methadone treatment (148), but this association was not replicated (149).…”

“…For example, the major allele of rs678849 has been associated with higher relapse rates among African American OUD patients undergoing buprenorphine treatment, as indicated by positive opioid urine tests (148, 149). Interestingly, the major allele was initially associated with lower relapse rates among African American OUD patients on methadone treatment (148), but this association was not replicated (149). Jones et al (147) reported an association between rs678849 and abstinence-induced opioid withdrawal severity; however, it did not withstand a multivariate analysis.…”