Searching for evidence of genetic mediation of opioid withdrawal by opioid receptor gene polymorphisms.

BACKGROUND: Previous research has identified many genetic polymorphisms that appear to mediate the effects of opioid drugs. However, the relationship between genetic polymorphisms and the severity of opioid withdrawal has not yet been characterized.

METHODS: Data were collected from 48 daily heroin users who previously completed a standardized abstinence-induced or naloxone-precipitated withdrawal procedure to assess opioid dependence. The total withdrawal severity score (based on the COWS) from this procedure was correlated with genotype information for variants of OPRM1 (rs1799971; rs6848893), OPRD1 (rs10753331; rs2234918; rs581111; rs678849; rs1042114), and OPRK1 (rs6473797; rs963549). Genotype and other participant variables (age, race, sex, duration of drug use, concomitant drug use, route of opioid use) were used as predictors.

RESULTS: Of these variables, those individually correlated with a p < .2 were entered into a multivariate regression in order to identify the most predictive model. Three polymorphisms were significantly associated with severity of abstinence-induced withdrawal (n = 19) in the bivariate analysis (R): OPRM1 rs6848893 (.45), OPRD1 rs10753331 (.03), and rs678849 (.08), but only the OPRM1 rs6848893 was retained in the multivariate model (p < .001). For participants who underwent naloxone-precipitated withdrawal (n = 29) only OPRK1 rs6473797 (-.23) was significant in the bivariate analysis, though not retained in the final model.

CONCLUSIONS: These data provide evidence for genetic modulation of opioid withdrawal severity, and suggest there may be qualitative differences between withdrawal resulting from abstinence and antagonist-precipitated withdrawal.

SCIENTIFIC SIGNIFICANCE: This study demonstrates the importance and feasibility of incorporating genetic information into clinical addiction research.