Opioid Receptor, mu OPRM1 Genotype, 1 Variant

Predicts response to opioid agents

Related Tests
  • Assesses genetic risk of abnormal drug metabolism for drugs metabolized by CYP2D6, CYP2C9, CYP2C19, and CYP3A5
  • May aid in drug selection and dose planning for many drugs
  • Single tests for CYP2D6, CYP2C9, CYP2C19, and CYP3A5 are available separately

Opioid agonists (eg, morphine, fentanyl) are typically administered for pain control and opioid antagonists (eg, naltrexone) are often prescribed for the treatment of alcohol and/or opioid dependency. Pharmacogenetic variation may affect pharmacokinetics or pharmacodynamics of a drug which may contribute to toxicity and risk for adverse drug reactions, including reduced therapeutic benefit.

The OPRM1 gene is associated with the pharmacodynamics of opioids. Variants in OPRM1 can result in different binding affinities to and clinical effects of opioids. The association of OPRM1 and drug sensitivity is not definitive and may be different for individual opioids. Testing should be performed for pretherapeutic identification of individuals who may require higher or lower doses of opioid drugs to achieve adequate pain control or have a better response to naltrexone for the treatment of alcohol and/or opioid dependency.

Genetics

Gene

OPRM1

Inheritance

Autosomal codominant

Penetrance

Drug dependent

Structure/Function

OPRM1 encodes the µ-opioid receptor 1 protein and is the primary binding site of action for various synthetic and endogenous opioids, including both agonists and antagonists. One of three opioid receptors is involved in this process. 

Alleles

The OPRM1 c.118A>G variant has an overall frequency of ~10.5% but varies by ethnicity :

  • African Americans: 1.5-4%  
  • Caucasians: 11-14%  
  • Hispanics: 14-24%  
  • Asians: 49-60% 

The c.118A>G variant results in 

  • Loss of a putative N-glycosylation site in the extracellular receptor region
  • Lower cell-surface receptor binding site availability compared to the A allele receptors
  • Thought to decrease mRNA and receptor protein concentrations
  • Lower sensitivity to opioid receptor agonists prescribed for pain control (eg, morphine)
  • Higher sensitivity to opioid receptor antagonists used in the treatment of alcohol and drug dependency (eg, naltrexone)

Test Interpretation

Sensitivity/Specificity

  • Clinical sensitivity/specificity: drug dependent
  • Analytical sensitivity/specificity: >99%

Results

Result Variant Detected Clinical Significance

Homozygous G/G

Two copies of OPRM1 c.118A>G variant detected

Genotype is consistent with decreased sensitivity to opioid agonists and increased sensitivity to opioid antagonists

Individual may require higher or more frequent doses of opioid agonists to achieve adequate pain control and may be more likely to respond to opioid antagonists in treatment of alcohol and/or opioid dependency

Heterozygous G/A

One copy of OPRM1 c.118A>G variant detected

Further studies are needed to determine clinical significance of this genotype, but it is possible that individual may require higher or more frequent doses of opioid receptor agonists to achieve adequate pain control and be more likely to respond to opioid antagonists in treatment of alcohol and/or opioid dependency

Homozygous A/A

No copies of OPRM1 c.118A>G variant detected

Further studies are needed to determine clinical significance of this genotype, but it is possible that individual may require higher or more frequent doses of opioid receptor agonists to achieve adequate pain control and may be more likely to respond to opioid antagonists in treatment of alcohol and/or opioid dependency

Limitations

  • OPRM1 variants other than c.118A>G are not evaluated by this test
  • Diagnostic errors can occur due to rare sequence variations
  • Risk of therapeutic failure or adverse reactions with opioids may be affected by genetic and nongenetic factors that are not detected by this test
  • Genetic testing does not replace the need for therapeutic or clinical monitoring

References