OPRM1 rs1799971 (A118G): What It May Mean for Pain and Opioid Response

The OPRM1 rs1799971 variant, also called A118G or Asn40Asp, is a common DNA difference in the gene that encodes the μ-opioid receptor. Because this receptor responds to the body’s natural opioid peptides and to opioid medications, researchers have studied the variant in relation to pain and opioid response [R, R].

Some studies have found small differences in opioid use or pain scores after surgery among people carrying the G allele. The findings depend on the clinical setting and are not strong enough to guide an individual’s medication or dose. The variant also cannot determine a person’s pain threshold or predict whether they will develop a substance use disorder. Some studies report statistical associations with substance-dependence outcomes across groups, but these do not translate into an individual prediction [R, R, R].

What Does the OPRM1 Gene Do?

The OPRM1 gene encodes the mu-opioid receptor, a protein found in the brain, spinal cord, and other tissues. It is activated by opioid peptides made in the body, including endorphins and enkephalins, as well as by opioid medicines [R].

When the receptor is activated, it helps transmit signals involved in pain modulation and other nervous-system functions. This is one reason OPRM1 has been studied in research on pain relief, reward, and responses to opioid drugs. The gene is one part of a larger system; receptor activity also depends on other genes, the medicine used, the dose, the person’s health, and the circumstances in which pain is treated.

What Is OPRM1 rs1799971?

The name A118G describes a change from A to G at a position in the OPRM1 coding sequence. This changes the receptor’s amino acid at position 40 from asparagine to aspartic acid, known as Asn40Asp or N40D. The change is located near a potential site for sugar attachment to the receptor [R, R].

Laboratory studies have examined whether this difference affects receptor expression, binding, or signaling. Early findings suggested changes in how the variant receptor responded to beta-endorphin, but experimental results have not produced a simple, consistent explanation for opioid response in people [R, R].

What Do AA, AG, and GG Mean?

These genotypes describe the two copies of rs1799971:

Genotype	What it means
AA	Two A alleles
AG	One A allele and one G allele
GG	Two G alleles

The G allele is the variant most often examined in studies of pain and opioid response. That does not mean every G-allele carrier will experience pain differently or respond differently to medication. Genotype is one small piece of a complex response.

What Does Research Say About Pain and Opioid Response?

The most useful evidence concerns pain and opioid use in specific clinical settings, particularly after surgery. A systematic review and meta-analysis published in 2023 found small associations between rs1799971 and acute postsurgical opioid use and pain scores. Its analyses included more than 8,000 people for opioid use and more than 4,000 for pain scores. The authors also found that most previously reported candidate-gene associations did not have enough consistent evidence for meta-analysis or failed to replicate [R].

A Clinical Pharmacogenetics Implementation Consortium guideline reviewed OPRM1 alongside other genes and described the evidence for using OPRM1 genotype in clinical care as limited or weak. It does not provide an OPRM1-based opioid dosing recommendation [R].

Research question	What the evidence supports
Does the G allele affect opioid use after surgery?	Some pooled studies report a small difference in acute postsurgical opioid use [R]
Does it affect pain sensitivity?	Small differences in pain scores have been reported in some acute postsurgical settings [R]
Can it guide opioid prescribing?	Current CPIC guidance says the OPRM1 evidence is limited or weak for clinical use and does not support changing a dose based on this marker alone [R]

Results can differ between studies because they involve different procedures, opioid medicines, doses, populations, pain measures, and follow-up periods. A finding in acute postsurgical pain does not automatically apply to chronic pain, cancer pain, labor, or another situation.

Does OPRM1 rs1799971 Predict Addiction?

No. OPRM1 is part of the body’s opioid signaling system, so researchers have studied rs1799971 in relation to substance use. A collaborative meta-analysis of 25 datasets and more than 28,000 people of European ancestry found a small paradoxical association between the G allele and lower odds of a broad measure of substance dependence (odds ratio 0.90). When the researchers examined individual substances, the associations were not statistically significant [R].

That finding describes a difference across a study population; it cannot tell whether one person will develop a substance use disorder. Risk is shaped by many factors, including personal and family history, environment, mental health, access to care, and exposure to addictive substances. rs1799971 is not a diagnostic test or an individual risk score.

Can This Variant Tell You Which Pain Medication to Take?

No. OPRM1 rs1799971 should not be used by itself to choose an opioid, set a dose, or decide whether a medication is safe. CPIC’s opioid guideline provides prescribing recommendations for certain medications based on CYP2D6 genotype, but describes the clinical data for OPRM1 as limited or weak [R].

Do not start, stop, or change a medication based on a raw DNA result. Medication decisions should be made with a qualified healthcare professional who can consider your health history, the specific medication, other medicines, and the clinical context.

Frequently Asked Questions

What is the OPRM1 A118G variant?

A118G is another name for rs1799971, a coding variant in OPRM1. It changes the receptor’s amino acid at position 40 from asparagine to aspartic acid.

Which OPRM1 allele is associated with opioid response?

Many studies have examined the G allele. Some find a small association with postsurgical opioid use or pain scores, but results vary by setting and are not reliable enough to predict one person’s response.

Does the GG genotype mean I have high pain sensitivity?

No. A genotype cannot determine your overall pain sensitivity. Research findings are small and context-dependent, and they do not predict how an individual will experience pain.

Does rs1799971 tell me whether I am at risk for addiction?

Research has found small, population-level associations for some substance-dependence outcomes, but rs1799971 cannot predict whether an individual will develop a substance use disorder.

Should my OPRM1 genotype change my medication dose?

No. Current clinical guidance does not support changing an opioid dose based on OPRM1 rs1799971 alone. Do not change medication without guidance from a healthcare professional.

Explore OPRM1 in GeneExplorer

OPRM1 rs1799971 is an interesting example of how one genetic variant can be biologically relevant while still having limited predictive value for an individual.

You can explore the OPRM1 marker in GenesUnveiled GeneExplorer to see the genotype found in supported raw DNA data and read its educational context.