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:

1. Current or former participation in an Archway methadone or buprenorphine
treatment study;

2. Age 18 or older;

3. Meet DSM-IV criteria for opioid dependence;

4. Self-identified as African American, with at least 3 African American
grandparents by self-report;

5. 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;

6. 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;

7. Able to speak and read English sufficiently to provide informed consent;

8. Former participants only: have consented to future contact .

EXCLUSION CRITERIA:

(1) Inability to give informed consent.