Effects of Single Nucleotide Polymorphisms on Surgical and Postsurgical Opioid Requirements: A Systematic Review and Meta-analysis

Abstract

Objectives: There is great heterogeneity in the way individuals respond to medications. Inherited differences, such as single nucleotide polymorphisms (SNP), can influence the efficacy and toxicity of drugs. This meta-analysis aims to collate data from studies investigating the effect of SNPs on postoperative and/or intraoperative opioid requirements. Materials and Methods: A meta-analysis was conducted following PRISMA guidelines. Eligibility criteria for studies included were reporting amount of postoperative and/or intraoperative opioid used as the primary outcome and genotyping patients for SNPs in one of the following genes; OPRM1, CYP2D6, CYP3A4, CYP3A5, COMT, UGT2B7, or ABCB1. A comprehensive systematic search for articles using keywords 'opioid-sensitivity,' 'polymorphisms,' 'post-operative opioid,' 'post-surgical opioid,' 'post-operative pain,' and 'post-surgical pain' was performed. Results: Fifty-one studies were included. Individuals homozygous for AA at the OPRMI (rs1799971) polymorphisms required less postsurgical opioid compared with those homozygous for GG (Hedges g, -0.270; 95% confidence interval, -0.433 to -0.108; P=0.001). Polymorphisms in CYP2D6, CYP3A4, CYP3A5, COMT, UGT2B7, and ABCB1 did not affect opioid requirements. Discussion: Investigation of single changes in 1 gene can only yield limited information regarding genetic effects on opioid requirements. Rapid development of whole genome sequencing enables information on all genetic modifications that may affect analgesic response to be collected. The information collected must include data on the individual's metabolic enzymes, as well as information on drug receptors and enzymes responsible for drug degradation, so that a personal profile can be built up which will predict individual response to drugs, and guide clinicians on the type and dosage of drug to use.