Despite reasonable statistical power we found no evidence of association between the five mu opioid receptor polymorphisms studied and severe opioid dependence in our sample. There were, however, significant allele frequency differences between African-Americans and European-Americans for all five polymorphisms, irrespective of drug-dependent status. Linkage disequilibrium analysis of the African-American genotypes indicated linkage disequilibrium (P<0.0001) across the five-polymorphism, 1911 base pair region. In addition, only four haplotypes of these five polymorphisms are predicted to exist in African-Americans.

Two polymorphisms of the human mu opioid receptor gene are described. A non-coding region polymorphism (G to T) occurs at nucleotide 175 preceding the initiation of translation. A coding polymorphism in exon 1 (C to T) at nucleotide 229 changes an alanine residue to a valine residue. Frequencies of these polymorphisms were examined in groups of cocaine and/or opioid dependent individuals and matched controls. There were no significant differences between groups, although a trend (p= 0.05) towards a higher frequency of the 229 valine allele was observed in the substance abuse group, suggesting a need for large, well-controlled studies of this polymorphism in severe substance abusers.

While methadone maintenance treatment (MMT) has been demonstrated to be an effective treatment for opiate dependence, its impact on the treatment outcome of other illicit drug abuse is not as clear. Using the initial urine drug screen (UDS) and follow-up UDS at 1, 6, 12, and 24 months, 167 patients consecutively admitted to MMT were evaluated for opiate, sedative (predominantly benzodiazepine), and stimulant (predominantly cocaine) use. Retention for the opiate only group was 97.32 days longer on average than for patients using opiates along with stimulants, sedatives, or both stimulants and sedatives. Patients abusing opiates only had the greatest decrease in drug use; however, MMT was also associated with decreases in cocaine and sedative use over the 24 month follow-up period. There was no evidence that patients "switched" their drugs of abuse with time in treatment. The negative impact of non-opiate drug use on outcome in MMT and its implications for treatment planning are discussed.

These data suggest that the PDYN repeat polymorphism should be studied in additional opioid-dependent populations.

The mu-opioid receptor (MOR) mediates reward and dependence associated with opioids and other commonly abused substances. Variability in the MOR gene, OPRM1, may influence risk for opioid dependence. In this study, associations between two single nucleotide polymorphisms (SNPs), dbSNP rs540825 and dbSNP rs562859, and opioid dependence were investigated. The two SNPs are located in the protein coding region of the novel exon X of an alternative splice variant of OPRM1, and can be detected using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) methods. Genotyping at the two SNPs was performed for 170 severe opioid dependent individuals and 128 carefully screened controls. Although no differences were found between cases and controls, there were significant prevalence differences between African-American (AA) subjects and European-American (EA) subjects for SNP 540825 allele and genotype frequencies. The 540825 and 562859 polymorphisms were found to be in complete linkage disequilibrium (LD) for both ethnic groups, and LD existed between the 562859 SNP and the A(-1320)G SNP in the promoter region of OPRM1 in AAs, based on genotyping data previously carried out on the same subjects. LD between these two markers, separated by 55 kb, links the entire distance studied in this project. The results indicate that polymorphisms in the novel splice variant are not associated with opioid dependence, but are in LD with other polymorphisms in OPRM1.