The Relevance of the OPRM1 118A>G Genetic Variant for Opioid Requirement in Pain Treatment: A Meta-Analysis.

BACKGROUND: There is obvious difference in individual response to opioids. Many studies have examined the correlation between the mu-opioid receptor 1 (OPRM1) 118A>G genetic variation and opioid requirement in pain treatment, but the conclusion remains elusive.

OBJECTIVES: To investigate whether the OPRM1 118A>G genetic variation is associated with the opioid requirement.

STUDY DESIGN: Systematic review and meta-analysis.

METHODS: PubMed, Cochrane library, and EMBASE databases were systematically searched up to May 5, 2018, using the keywords "OPRM1," "genetic variant," "opioid," and "pain" to identify reviews or meta-analyses on this topic. Two independent reviewers performed the data extraction and assessed study quality. The authors investigated the standardized mean difference (SMD) of opioid requirement between AA homozygotes and G allele carriers. The authors also examined the association between the OPRM1 118A>G genetic variation and adverse effects such as nausea and vomiting. Potential bias was assessed using the Egger's test and the Begg's test.

RESULTS: A total of 530 articles were retrieved from the databases searched, and 36 studies involving 8,609 patients were included in the final analysis. G allele carriers required a higher mean opioid dose (SMD: 0.17; 95% confidence interval [CI]: [0.12, 0.22]; P < 0.001) and displayed less nausea risk difference (RD): -0.04; 95% CI: [-0.06, -0.01]), but the incident rate of vomiting has no relationship with the genetic variant than AA homozygotes in a random-effects meta-analysis. Although there was no evidence of publication bias (Begg's test: P = 0.333; Egger's: P = 0.561), heterogeneity was present among studies (I-squared = 54.3%). In the subgroup meta-analyses, there was also significance observed in the postoperative pain setting.

LIMITATIONS: In all of the articles reviewed, postoperative pain and cancer pain were mostly discussed except for one in other pain setting.

CONCLUSIONS: In this meta-analysis, the results indicate the OPRM1 A118G polymorphism was associated with the opioid requirement and the adverse effects in pain treatment especially in postoperative pain. This may provide valuable information for clinicians to adopt personalized pain management by properly using the opioids in individual patients.

KEY WORDS: OPRM1, genetic variation, opioid, pain, side effect, review, meta-analysis.