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Effects of Single Nucleotide Polymorphisms on Surgical and Post-surgical Opioid Requirements - A Systematic Review and Meta-analysis.

Choi, Siu-Wai PhD; Lam, David M.H. MbChB; Wong, Stanley S.C. MD, MBBS; Shiu, Haydn H.C. MSc; Wang, Amy X.M. PhD; Cheung, Chi-Wai MD, FHKCA, FHKAM
Clinical Journal of Pain: Post Acceptance: April 4, 2017
doi: 10.1097/AJP.0000000000000498
Review Article: PDF Only

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 post-operative and/or intra-operative opioid requirements.

Methods: This meta-analysis was conducted following PRISMA guidelines. Eligibility criteria for studies in this meta-analysis were reporting amount of post-operative and/or intra-operative 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 post-surgical opioid compared to those homozygous for GG (Hedge's g -0.270, 95%CI -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 one gene can only yield limited information regarding genetic effects on opioid requirements. Rapid development of whole genome sequencing enables information on all genetic modifications which 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.

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