Impact of Delta Opioid Receptor Gene (OPRD1) Variations on Treatment Outcome in African Americans

The NIDA Clinical Trials Network s (CTN) START Study was designed to look at the pharmacogenetics of treatment response. The CTN investigators found that an intronic SNP (rs678849) in the gene for the opioid delta-1 receptor (OPRD1) strongly predicted treatment response in African-Americans. Specifically, during treatment with methadone, African-Americans with one variant of the SNP (CC) were less likely to use illicit opioids compared to African-Americans with other variants of the SNP (CT or TT) (relative risk = 0.53, 95% CI 0.46-0.60, p = 0.001). During treatment with buprenorphine, the association was reversed: African-Americans with the CC variant were more likely to use illicit opioids, compared to those with the CT or TT variants (relative risk = 2.13, 95% CI 1.81-2.45, p = 0.012). This pattern of findings was unexpected, both in terms of racial specificity and differential drug associations. Replication in a new sample is crucial to determining whether it represents a real effect.

Study objectives include: (1) To independently replicate the pharmacogenetic NIDA CTN findings by comparing urine drug screen opioid results for rs678849 genotype groups among opioid-addicted African-American individuals, treated with either buprenorphine or methadone; (2) To determine whether any effect of rs678849 genotype varies by demographic, drug use, mental health, and psychosocial characteristics; (3) To determine whether any effect of rs678849 genotype extends to cocaine use, and (4) To examine haplotype blocks in OPRD1 that might help explain the association.

We will recruit a sample of n=135 (to obtain 130 completers; 65 methadone, 65 buprenorphine) current and former participants in Archway treatment studies in order to have power of 0.80 to detect a difference of 0.5 standard deviations between rs678849 genotypes. To be eligible, participants must have received a stable dose (no taper > 7 days in length) of buprenorphine or methadone for at least 12 weeks and had at least 10 weekly urine drug screens during that time. After informed consent, in an approximate 3-hour session, participants will undergo collection of blood or a buccal swab for DNA extraction and analysis (blood is preferred, but buccal extraction enables inclusion of participants with poor venous access) and will complete 3 questionnaires; the Addiction Severity Index, the Perceived Neighborhood Scale, and sections of the Diagnostic Instrument for Genetic Studies.

• INCLUSION CRITERIA:

• Current or former participation in an Archway methadone or buprenorphine treatment study;
• Age 18 or older;
• Meet DSM-IV criteria for opioid dependence;
• Self-identified as African American, with at least 3 African American grandparents by self-report;
• At least 12 weeks of continuous treatment with a stable dose (no taper >7 days in length) of either buprenorphine or methadone, in a treatment regimen in which the physician considers dose increases in response to withdrawal symptoms, craving, or evidence of illicit opioid use by urine screens;
• At least 10 weeks of urine results available for analysis in that 12-week period, with no more than 6 consecutive urine data points missing, a requirement that should limit non-compliance as a factor;
• Able to speak and read English sufficiently to provide informed consent;
• Former participants only: have consented to future contact .

Exclusion criteria

(1) Inability to give informed consent.