Opioid receptor response (OPRM1 A118G)

OPRM1 builds the main receptor that opioids and the body's own endorphins act on. A common variant (118G) can subtly change pain relief from opioids and the response to the alcohol-treatment drug naltrexone. It mainly matters in those specific situations.

What the OPRM1 A118G variant does

OPRM1 makes the mu-opioid receptor, the target of morphine, oxycodone, fentanyl, heroin and the body's own endorphins. This variant changes one amino acid in the receptor's extracellular region, and laboratory work suggests it alters receptor expression and binding affinity somewhat.

Because the receptor sits at the centre of pain relief, reward and dependence, the variant has been studied in all three, which is also why the literature around it is unusually messy.

How strong the evidence is, which is the point of this page

Weaker than its popularity suggests. In a study of 302,585 people, the variant was associated with opioid use disorder at an odds ratio of about 0.89 per copy, a small effect detectable only at that scale. ClinVar classifies it as uncertain significance with no review-status stars.

The more commonly repeated claim, that carriers need higher opioid doses for the same pain relief, has been reported and contradicted across many small studies, and no pharmacogenetic body has issued an actionable dosing recommendation for OPRM1. Where CPIC does give opioid guidance, it is for CYP2D6 and codeine or tramadol, a different gene and a different mechanism.

How common it is

This is ordinary variation, and its distribution is striking: in 1000 Genomes reference data about 48% of East Asian-ancestry individuals carry one copy and 17% carry two, against roughly 22% and 2% in European-ancestry samples and under 5% in African-ancestry ones.

A variant carried by two thirds of one population and a fifth of another, with effects this small, is not going to explain individual differences in how a person responds to painkillers.

What this variant does not tell you

It does not predict your response to a specific opioid, your risk of addiction, or how much pain relief you will need after surgery. Those depend on the type of pain, previous exposure, other medicines, kidney and liver function, anxiety and sleep, and on CYP2D6 for the drugs that need activating.

Addiction risk in particular is shaped far more by circumstance, mental health, exposure and how a drug is prescribed than by any single receptor variant. Treat this result as biology of interest rather than as information about yourself.

What each rs1799971 genotype means

rs1799971 has three possible genotypes: AA, AG and GG.

Typical opioid response (rs1799971 AA). You have the common version of OPRM1, the main opioid receptor, so as far as this gene goes, your response to opioid pain medicines and to your own endorphins is in the typical range. This only matters if you ever need opioids or the alcohol-treatment drug naltrexone.

One 118G copy (OPRM1) (rs1799971 AG). You carry one copy of the OPRM1 118G variant, which can subtly reduce how much pain relief you get from opioids (sometimes needing a slightly higher dose) and may affect response to the alcohol-treatment drug naltrexone. It only matters in those specific situations.

Two 118G copies (OPRM1) (rs1799971 GG). You have two copies of the OPRM1 118G variant, more common in people of East Asian ancestry. It's linked to somewhat reduced opioid pain relief (possibly higher dose needs) and an altered response to naltrexone for alcohol use. This is informational and only relevant around those medications.

Evidence & sources

Across global populations, about 3% of people carry two copies of this variant, and about 73% carry none.

This variant appears in 6 published genetic studies: PubMed 32492095 · PubMed 35879402 · PubMed 36171425 · PubMed 36207451 · PubMed 37156939 · PubMed 37250466.

Common questions

Do I need more painkillers because of this variant? There is no reliable evidence that you do. Studies of opioid dose requirements and this variant have gone in both directions, and no clinical guideline recommends adjusting opioid dosing on OPRM1 genotype.

Does this variant mean I am at risk of opioid addiction? No. The measured association with opioid use disorder is around 0.89 per copy in a study of 300,000 people, which is both small and in the protective direction. Dependence risk is driven overwhelmingly by exposure and circumstance.

Related

Abacavir hypersensitivity (HLA-B*57:01) · Drug acetylation speed (NAT2) · Fluoropyrimidine (5-FU) toxicity risk · Hepatitis C treatment response (IL28B) · Statin-induced myopathy risk · Tacrolimus metabolism (CYP3A5 gene) · Thiopurine metabolism (TPMT and NUDT15 genes)