Work

Kappa-opioid receptor gene (OPRK1) variations associated with opioid abstinence behaviors among chronic heroin users

Year: 2025

Type: article

Abstract: Introduction Research suggests kappa -opioid receptors (KORs) modulate drug use and stress-related behaviors. While some findings indicate KORs could influence initial susceptibility to opioid use disorder (OUD), few studies have examined whether variations in the gene encoding the receptor ( OPRK1 ) relate to clinically-relevant behavioral variation among current opioid users. This study examined whether OPRK1 polymorphisms predicted opioid-abstinence phenotypes in three separate but conceptually-linked aims: (1) retrospective self-report of number of lifetime heroin-quit attempts at screening, (2) prospective assessment of opioid-abstinence initiation during a two-week buprenorphine (8 mg/day sublingual) outpatient stabilization period, and (3) prospective assessment of opioid lapse during a three-week buprenorphine dose-tapering outpatient period (4-mg/day, 2-mg/day and 0-mg/day during weeks 1-3, respectively). Methods OPRK1 genotype and opioid-abstinence phenotype data (urinalysis and self-report) were obtained from current regular heroin users. Genotype-phenotype analyses controlled for self-identified race and heroin-use duration. Results OPRK1 rs7817710 (intron) T/T homozygotes ( n = 145) reported significantly more heroin-quit attempts than G/T heterozygotes ( n = 86) or G/G -homozygotes ( n = 35). During outpatient buprenorphine stabilization, OPRK1 rs6989250 (intron) C/C homozygotes ( n = 43) provided a significantly lower proportion of opioid-free urine samples than G -allele carriers ( n = 7). During buprenorphine dose tapering, OPRK1 rs3802281 (3’UTR) C-allele carriers ( n = 21) and rs7817710 G -allele carriers ( n = 11) lapsed to opioid use significantly more slowly than T/T homozygotes at either locus ( n = 17 and n = 16, respectively). The rs3802281–rs7817710 haplotype block was associated with Experiment 1 binary phenotypes. Conclusion These findings implicate OPRK1 genetic variation in several opioid-abstinence phenotypes. These results, if replicated, could improve understanding of the course and treatment of OUD.

Source: Frontiers in Pharmacology

DOI: 10.3389/fphar.2025.1714546

Authors: Mark K. Greenwald, Catherine Demery, Tabitha E. H. Moses, Margit Burmeister

Institutions: Wayne State University, University of Michigan

Language: English

Topic: Opioid Use Disorder Treatment

Subfield: Public Health, Environmental and Occupational Health

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $3,801