The association of genetic polymorphisms in the κ-opioid receptor 1 gene with body weight, alcohol use, and withdrawal symptoms in patients with methadone maintenance

J Clin Psychopharmacol. 2014 Apr;34(2):205-11. doi: 10.1097/JCP.0000000000000082.

Abstract

Methadone is a synthetic opioid that binds to the κ-opioid receptor with a low affinity. This study tested the hypotheses that the genetic polymorphisms in the κ-opioid receptor 1 (OPRK1) gene region are associated with methadone treatment responses in a Taiwan methadone maintenance treatment (MMT) cohort. Seventeen single nucleotide polymorphisms (SNPs) in OPRK1 were selected and genotyped on DNA of 366 MMT patients. Six SNPs from rs7843965 to rs1051660 (intron 2 to exon 2) were significantly associated with body weight (P < 0.007). A haplotype of 4 SNPs rs7832417-rs16918853-rs702764-rs7817710 (exon 4 to intron 3) was associated with bone or joint aches (P ≤ 0.004) and with the amount of alcohol use (standard drinks per day; global P < 0.0001). The haplotype rs10958350-rs7016778-rs12675595 was associated with gooseflesh skin (global P < 0.0001), yawning (global P = 0.0001), and restlessness (global P < 0.0001) withdrawal symptoms. The findings suggest that genetic polymorphisms in OPRK1 were associated with the body weight, alcohol use, and opioid withdrawal symptoms in MMT patients.

Publication types

  • Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Alcohol Drinking / genetics*
  • Body Weight / genetics*
  • Genetic Association Studies
  • Haplotypes
  • Heroin Dependence / drug therapy
  • Humans
  • Methadone / adverse effects*
  • Methadone / pharmacokinetics
  • Methadone / therapeutic use*
  • Opiate Substitution Treatment / adverse effects*
  • Polymorphism, Single Nucleotide / genetics*
  • Receptors, Opioid, kappa / genetics*
  • Substance Withdrawal Syndrome / genetics*
  • Taiwan
  • Young Adult

Substances

  • OPRK1 protein, human
  • Receptors, Opioid, kappa
  • Methadone