title: The impact of genetic variation on sensitivity to opioid analgesics in patients with postoperative pain: a systematic review and meta-analysis.
abstract: BACKGROUND
  Individual response to opioid analgesics varies among patients.
  
  
  OBJECTIVE
  This study sought to clarify the impact of distinct genetic variations on pain, opioid consumption, and opioid side effects in patients with postoperative pain.
  
  
  METHODS
  A systematic review and meta-analysis of associations between genetic single-nucleotide polymorphisms (SNPs) and opioids used for acute postoperative pain.
  
  
  METHODS
  This meta-analysis examined all studies involving an association between genetic polymorphisms and the analgesic efficacy or clinical outcome of opioid analgesics for postoperative pain.
  
  
  METHODS
  A literature search was performed up to January 31, 2014, using the PubMed, EMBase, ISI Web of Science, and Cochrane Library databases.
  
  
  RESULTS
  Fifty-nine studies were included in this systematic review, and 23 studies (a total of 5,902 patients) were included in the final meta-analysis. The results showed that human μ-opioid receptor gene (OPRM1) 118G allele variant carriers consumed more opioids for analgesia (SMD = -0.17, 95% CI = [-0.25, -0.10], P < 0.00001), but reported higher pain scores (MD = -0.11, 95% CI = [-0.17, -0.04], P = 0.002) and less nausea and vomiting (odds ratio = 1.30, 95% CI = [1.08, 1.55], P = 0.005) than the homozygous 118AA patients during the first 24 hour but not the 48 hour postoperative period. Moreover, CYP3A4*1G carriers consumed less opioids than homozygous CYP3A4*1/*1 patients during the first 24 hours postoperative period (MD = 45.12, 95% CI = [36.17, 54.06], P < 0.00001). No significant differences were found in CYP3A5*3, ABCB1 C3435T, and G2477T/A genetic polymorphisms.
  
  
  CONCLUSIONS
  Some potential non-genetic factors can modify the effects of gene SNP on pain and opioid consumption during the postoperative period, such as age, gender, mood, anxiety, and drug-drug interactions. But further analyses could not be performed in the present meta-analysis due to limited information.
  
  
  CONCLUSIONS
  The results indicate that among the genetic SNPs we studied which include those affecting analgesic drug metabolism, transport of analgesic agents across the blood-brain barrier, and their activity at target receptors and ion channels and in the modulation of neurotransmitter pathways, the A118G allele variant of OPRM1 has the most potent influence on pain management of postoperative patients. Opioid receptor gene information may provide valuable information for clinicians to properly manage the analgesic use of opioids individually for better pain management.
authors: Department of Pharmacy, Peking University Third Hospital, Beijing 100191, China; Peking University Sixth Hospital/Institute of Mental Health and Key Laboratory of Mental Health, Peking University, Beijing, China.
authors: Zhen-Yu
authors: ZY
authors: Ren
authors: Xiao-Qing
authors: XQ
authors: Xu
authors: Yan-Ping
authors: YP
authors: Bao
authors: Jie
authors: J
authors: He
authors: Le
authors: L
authors: Shi
authors: Jia-Hui
authors: JH
authors: Deng
authors: Xue-Jiao
authors: XJ
authors: Gao
authors: Hui-Lin
authors: HL
authors: Tang
authors: Yu-Mei
authors: YM
authors: Wang
authors: Lin
authors: L
authors: Lu
mesh_terms: D000701:Analgesics, Opioid / Q000009:adverse effects / Q000627:therapeutic use*; D005260:Female; D014644:Genetic Variation / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D059408:Pain Management / Q000379:methods; D010149:Postoperative Pain / Q000188:drug therapy* / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D016032:Randomized Controlled Trials as Topic / Q000379:methods; D017450:Receptors, Opioid, mu / Q000235:genetics*
chemical_list: D000701:Analgesics, Opioid; C485764:OPRM1 protein, human; D017450:Receptors, Opioid, mu