What is OPRM1?
The mu opioid receptor is a G protein-coupled receptor coded by the OPRM1 gene. It is the primary site of action for various endogenous and exogenous opioids.1 The most commonly studied single nucleotide polymorphism (SNP) of the OPRM1 gene is the A118G variant, or rs1799971, located on chromosome 6q25.2.2 This mutation causes an amino acid change from asparagine to aspartic acid.3 This was originally thought to cause a difference in beta endorphin binding affinity.1 However, subsequent data show no difference in binding affinity4–6, but do suggest a reduction in receptor expression,6–8. This SNP has been shown to affect individual response to opioids.
What do the data say about opioid response?
We reviewed 23 articles that studied the association between the A118G variant and opioid response. Most studies examined postoperative analgesic requirements as the primary outcome. Of the articles reviewed, 14 studies (n = 2936) showed carriers of the G allele for the A118G variant (and in particular homozygous carriers) had a decreased response to opioid administration.9–22 Nine studies (n = 1105) showed no difference in opioid response between those with the G allele and those with the wild type allele, although several of these studies attributed this to the low number of G/G study subjects.23–31
What do the data say about opioid-induced adverse effects?
Of the 29 articles reviewing the association between A118G and opioid-induced adverse effects, no association could be determined for most adverse effects such as pruritus, nausea, and vomiting. However, several studies have suggested that these patients may be no more protected against respiratory depression (RD) than patients with the normal genotype, while some studies show higher rates of RD among G carriers.12,19,32 This is obfuscated by several conflicting studies.20,33,34.
What do the data say about opioid dependence?
We reviewed 14 articles that studied the association between the A118G variant and opioid dependence. Of the 14 articles reviewed, 4 studies (n = 432) showed carriers of the G allele for the A118G variant had increased susceptibility to opioid dependence.35–38 Ten articles (n = 3,922) found no association between the A118G SNP and opioid dependence.28,39–47
A large body of data demonstrates an association between OPRM1 genotype and opioid requirements to achieve appropriate analgesia for acute pain. Patients exhibiting a lack of response to opioids are often prescribed higher doses of opioids to control their pain. The consequent assumption is that patients carrying the OPRM1 A118G SNP should also be prescribed higher doses of narcotics. However, given the aforementioned lack of clear data on risk of
opioid-induced respiratory depression in this population, caution and more frequent monitoring is highly advised if higher doses are considered among patients carrying the G allele. Other non-opioid therapies (e.g. NSAIDs, muscle relaxants etc.) should be thoroughly considered in this group. No association was found between OPRM1 and opioid dependence.
This literature search was conducted within the PubMed and Google Scholar databases. Results were limited to studies written in English, performed on human subjects, and focused on opioid response, dependence, and adverse effects.
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