Article Title

Association of OPRM1 Polymorphisms With DSM-5–Defined Prescription Opioid Use Disorder Among Chronic Pain Patients on Opioid Therapy for Noncancer Pain

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prescription opioid use disorder, chronic pain patients


Background/Aims: The OPRM1 118A>G polymorphism (rs1799971) has been associated with susceptibility to drug misuse. Previously we assessed the association between single nucleotide polymorphisms (SNPs) located in OPRM1 genetic locus, including rs1799971 and rs6923231, and susceptibility to substance misuse among outpatients receiving long-term opioid therapy.

Methods: We identified outpatients receiving opioid therapy for noncancer pain within a large health care system using electronic health records. Patients included those 18+ years old who received opioids for 4+ months in the past 12 months. We completed diagnostic interviews with 705 subjects to identify substance use disorders including opioid use disorder and history of illicit drug use. Genotyping was performed on an Applied Biosystems™ 7500 real-time polymerase chain reaction platform, using TaqMan™ kits.

Results: Mean age of patients was 55 years (SD: 13.4), and 60.9% (95% confidence interval [CI]: 55.9–65.7) were female. Based on Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) criteria, the lifetime prevalence of opioid dependence was 35.6% (95% CI: 32.1–39.1). Lifetime illicit drug use was 12.8% (95% CI: 10.3–15.2) for cocaine and 14.9% (95% CI: 12.3–17.5) for amphetamines/methamphetamines. Using ordinal logistic regression that controlled for age, gender, education and marital status, lifetime opioid use disorder by DSM-5 criteria (classified: none, mild, moderate, severe) was associated with the carriers of the G allele (coded 0, 1 or 2) at SNP rs6923231 (odds ratio: 1.48, P = 0.002), but the OPRM1 118A>G polymorphism (rs1799971) was not associated (P = 0.544). Multivariate linear regressions suggested the number of days the patient used cocaine (range: 0–100 days) was significantly associated with SNP marker rs6923231 (β = 0.72, P = 0.0000565), as was the number of days the patient used amphetamines/methamphetamines (range: 0–500 days; β = 0.09, P = 0.046). When we assessed opioid disorders based on DSM-IV criteria, neither SNP marker rs6923231 nor rs1799971 was associated.

Conclusion: We detected genetic liability for addiction based on the DSM-5 criteria at the OPRM1 genetic locus for SNP rs6923231, a previously unreported polymorphism for drug misuse. Since the SNPs for this study were identified using a tagging algorithm that was correlated with addiction phenotypes, SNP rs6923231 is likely a valid marker for addiction liability. To our knowledge, this is the first study to report genetic associations for OPRM1 variants based on the DSM-5 criteria for prescription opioid use disorder.