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FeedbackPolymerase Chain Reaction (PCR)/Fluorescence Monitoring
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 approximately 10.5% but varies by ethnicity :
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
- Analytic 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
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NIH - OPR1 gene
National Institutes of Health, U.S. National Library of Medicine. Genetics Home Reference: OPRM1 gene. Reviewed Nov 2017; accessed Apr 2020.
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OMIM - OPRM1
Online Mendelian Inheritance in Man (OMIM).Opioid receptor, mu-1; OPRM1. Edited Jan 2017; accessed Apr 2020.
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9689128
Bond C, LaForge KS, Tian M, et al. Single-nucleotide polymorphism in the human mu opioid receptor gene alters beta-endorphin binding and activity: possible implications for opiate addiction. Proc Natl Acad Sci U S A. 1998;95(16):9608‐9613.
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11134674
LaForge KS, Yuferov V, Kreek MJ. Opioid receptor and peptide gene polymorphisms: potential implications for addictions [published correction appears in Eur J Pharmacol 2001 Aug 24;426(1-2):145]. Eur J Pharmacol. 2000;410(2-3):249‐268.
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19528658
Mague SD, Isiegas C, Huang P, et al. Mouse model of OPRM1 (A118G) polymorphism has sex-specific effects on drug-mediated behavior. Proc Natl Acad Sci U S A. 2009;106(26):10847‐10852.
Predicts response to opioid agents