title: Meta-analysis of the relevance of the OPRM1 118A>G genetic variant for pain treatment.
abstract: Regard of functional pharmacogenetic polymorphisms may further the success of pain therapy by adopting individualized approaches. The mu-opioid receptor gene (OPRM1) 118A>G polymorphism is a promising candidate for both opioid effects and pain because of both biological reasonability and apparent experimental and clinical evidence. We analyzed its importance for pain therapy using a meta-analytic approach to studies relating it to opioid pain therapy. Data from suitable studies selected from hits of a PubMed search for "OPRM1" were independently extracted by two authors. The meta-analysis included phenotypes by OPRM1 genotype (opioid dosing, pain, and side effects), publication year, diagnostic status, proportion of male study participants, and whether genotype frequencies agreed with Hardy-Weinberg equilibrium. We found no consistent association between OPRM1 118A>G genotypes and most of the phenotypes in a heterogeneous set of eight clinical studies. Only weak evidence of an association with less nausea (effect size, Cohen's d=-0.21, p=0.037) and of increased opioid dosage requirements (d=0.56, p=0.018) in homozygous carriers of the G allele was obtained. This indicates that despite initially promising results, available evidence of the clinical relevance of the OPRM1 118A>G polymorphism does not withhold a meta-analysis. This discourages basing personalized therapeutic concepts of pain therapy on OPRM1 118A>G genotyping at the present state of evidence.
authors.affiliation: pharmazentrum frankfurt/ZAFES, Institute for Clinical Pharmacology, Goethe University, Theodor Stern Kai 7, D-60590 Frankfurt am Main, Germany.
authors.forename: Carmen
authors.initials: C
authors.lastname: Walter
authors.forename: Jörn
authors.initials: J
authors.lastname: Lötsch
mesh_terms: D000701:Analgesics, Opioid / Q000009:adverse effects / Q000627:therapeutic use*; D003627:Data Interpretation, Statistical; D014644:Genetic Variation; D006801:Humans; D010146:Pain / Q000188:drug therapy* / Q000235:genetics*; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D017450:Receptors, Opioid, mu / Q000235:genetics*
chemical_list: D000701:Analgesics, Opioid; C485764:OPRM1 protein, human; D017450:Receptors, Opioid, mu
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