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Published on: March 8, 2020

Association of OPRD1 polymorphisms with heroin dependence in a large case-control series

Elliot C Nelson1, Michael T Lynskey, Andrew C Heath

  • 1Department of Psychiatry, Washington University School of Medicine, St. Louis, MO, USA Queensland Institute of Medical Research, Australia National Drug and Alcohol Research Centre, University of New South Wales, Australia Burnet Institute, Centre for Health Policy, Programs and Economics, School of Population Health, University of Melbourne, Australia.

Addiction Biology
|April 17, 2012
PubMed

Insights

Genetic variations in the OPRD1 gene are linked to an increased risk of heroin dependence. Specific OPRD1 single nucleotide polymorphisms (SNPs) and a GA haplotype show significant association with heroin use liability.

Area of Science:

  • Neurogenetics
  • Addiction Psychiatry
  • Pharmacogenomics

Background:

  • Opioid receptor genes (OPRM1, OPRD1, OPRK1) are implicated in heroin dependence risk.
  • Previous genetic association studies had limitations in sample size, SNP coverage, and yielded inconsistent results.

Purpose of the Study:

  • To investigate the association between single nucleotide polymorphisms (SNPs) in opioid receptor genes and heroin dependence.
  • To replicate and extend previous findings on the genetic underpinnings of heroin dependence liability.

Main Methods:

  • Genotyping of 136 SNPs across OPRM1, OPRD1, and OPRK1 genes in a large Australian cohort.
  • Comparison of heroin-dependent cases (N=1459) with non-dependent controls (N=1495) and neighborhood controls (N=531).
  • Statistical analysis including principal components analysis for admixture and haplotype analysis.

Main Results:

  • Replication of a significant association between four OPRD1 SNPs and heroin dependence, notably rs2236857 (OR 1.25; P=2.95×10(-4)).
  • Identification of a significant association between the OPRD1 GA haplotype (rs2236857 and rs581111) and increased heroin dependence risk (OR 1.68; P=1.41×10(-5)).
  • No significant associations were found for OPRM1 or OPRK1 SNPs with heroin dependence.

Conclusions:

  • Strong evidence supports the implication of OPRD1 SNPs, particularly the rs2236857-rs581111 GA haplotype, in the genetic liability for heroin dependence.
  • The findings replicate prior research and highlight OPRD1 as a key gene in opioid addiction.
  • No significant association was found for OPRM1 or OPRK1 gene variants in this study population.
Keywords:
Association studyOPRD1OPRK1OPRM1case-controlheroin dependence

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