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µ-opioid receptor gene variant OPRM1 118 A > G: a summary of its molecular and clinical consequences for pain. Review

 
: Walter, C.; Doehring, A.; Oertel, B.G.; Lötsch, J.

:

Pharmacogenomics 14 (2013), No.15, pp.1915-1925
ISSN: 1462-2416
English
Journal Article
Fraunhofer IME ()

Abstract
The human mu-opioid receptor variant 118 A>G (rs1799971) has become one of the most analyzed genetic variants in the pain field. At the molecular level, the variant reduces opioid receptor signaling efficiency and expression, the latter probably via a genetic-epigenetic interaction. In experimental settings, the variant was reproducibly associated with decreased effects of exogenous opioids. However, this translates into very small clinical effects (meta-analysis of 14 studies: Cohen's d = 0.096; p = 0.008), consisting of slightly higher opioid dosing requirements in peri- and post-operative settings. An effect can neither be maintained for chronic analgesic therapy nor for opioid side effects. It seems unlikely that further studies will reveal larger effect sizes and, therefore, further analyses appear unwarranted. Thus, due to its small effect size, the SNP is without major clinical relevance as a solitary variant, but should be regarded as a part of complex genotypes underlying pain and analgesia.

: http://publica.fraunhofer.de/documents/N-275375.html