Pharmacogenomics of the Human µ-Opioid Receptor

Kasai, Shinya; Ikeda, Kazutaka

doi:10.2217/pgs.11.68

Cited by 59 publications

(57 citation statements)

References 175 publications

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“…The OPRM1 gene encoding MOPR is a major candidate for genetic diversities of opioids; it has been also extensively discussed in a variety of populations (Uhl et al, 1999;Kasai et al, 2011). MOPR, a member of G-protein-coupled receptor (GPCR) family, is a key target factor playing important roles in analgesia, tolerance and dependency effects interacting with G-proteins (Gi/Go).…”

Section: Discussionmentioning

confidence: 99%

Gene Polymorphisms of OPRM1 A118G and ABCB1 C3435T May Influence Opioid Requirements in Chinese Patients with Cancer Pain

Gong¹,

Wang²,

Liu³

et al. 2013

Asian Pacific Journal of Cancer Prevention

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Section: Discussionmentioning

confidence: 99%

Gene Polymorphisms of OPRM1 A118G and ABCB1 C3435T May Influence Opioid Requirements in Chinese Patients with Cancer Pain

Gong¹,

Wang²,

Liu³

et al. 2013

Asian Pacific Journal of Cancer Prevention

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“…Our results add to the growing literature over the past decade that implicate a handful of promising single nucleotide polymorphisms (SNPs) of the mu opioid receptor gene (OPRM1) as candidates for clinically relevant variability in baseline mesolimbic reward neurobiology (dopamine-opioid interaction), opioid sensitivity, and addiction [1]. Our findings warrant further research to understand the mechanisms underlying specific at-risk overdose populations.…”

mentioning

confidence: 53%

On the Role of Genetic Testing for Personalized Drug Overdose Management

et al. 2013

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Author Reply: We thank our colleagues for their interest in our study entitled "Opioid Receptor Polymorphism A118G Associated with Clinical Severity in a Drug Overdose Population." Our results add to the growing literature over the past decade that implicate a handful of promising single nucleotide polymorphisms (SNPs) of the mu opioid receptor gene (OPRM1) as candidates for clinically relevant variability in baseline mesolimbic reward neurobiology (dopamine-opioid interaction), opioid sensitivity, and addiction [1]. Our findings warrant further research to understand the mechanisms underlying specific at-risk overdose populations. We completely concur that results of our pilot study, as with all such investigations, will require validation in larger populations, an effort which is currently being addressed at our institution. Confirming our results would have significant impact in the field of addiction to pave the way for personalized prescription practices not only for opioids, but for those at risk for drug overdose.Our data which demonstrated higher overdose severity in G allele subjects, not limited to opioid drugs, is likely due to dopamine-opioid interactions in the mesolimbic/striatal pathways relevant to reward and habit formation. Indeed, several lines of evidence have established significant disturbances of the opioid system in association with various drugs of abuse [2,3]. We therefore chose not to limit the analysis to only opioids given the biologic plausibility of enhanced abuse and addiction behaviors which apply for all drugs, not limited to opioids. To address our colleagues' suggestion to eliminate sympathomimetics, such as cocaine, from the analysis, we would argue that it is equally plausible that OPRM1 variants affect the same reward pathways for sympathomimetics, and thus arbitrary removal of these exposures would actually introduce, not eliminate, bias.A question was also raised as to whether the 118G allele confers resistance rather than increased susceptibility as suggested by the findings of our study. Consistent with the results of our study, multiple investigations have reported an

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“…Clinical studies report an increased expression of the MOR in cancer specimens and suggest an association with aggressiveness [39,40]. Recent attention has focused on the human l-opioid receptor gene (OPRM1) single nucleotide polymorphism (SNP) A118G, the most common genetic variation in the MOR which results in decreased sensitivity to analgesia and increased morphine requirements [41]. Breast cancer patients with the G allele were shown to have longer breast cancer-specific survival [42].…”

Section: Involvement Of Opioid Receptors In the Effect Of Opioids On mentioning

confidence: 99%

Opioid Analgesic Agents and Cancer Cell Biology

Xie

Parat

2015

Curr Anesthesiol Rep

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There is growing interest in the notion that perioperative factors may influence the long-term outcome of cancer surgery. Among these factors, pharmacologic agents including anesthetics and analgesics have been scrutinized for their potential effect on tumors. Opioids are particularly interesting in this context, as conflicting literature reports both pro-and anti-tumor effects for this class of drugs in every aspect of tumor growth and metastasis that has been examined. Cancer and non-cancer cells important to the tumor biology may be affected, as demonstrated using a variety of in vitro and preclinical models. More evidence is required to optimize the perioperative pain management of cancer surgery patients.

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Pharmacogenomics of the Human µ-Opioid Receptor

Cited by 59 publications

References 175 publications

Gene Polymorphisms of OPRM1 A118G and ABCB1 C3435T May Influence Opioid Requirements in Chinese Patients with Cancer Pain

Gene Polymorphisms of OPRM1 A118G and ABCB1 C3435T May Influence Opioid Requirements in Chinese Patients with Cancer Pain

On the Role of Genetic Testing for Personalized Drug Overdose Management

Opioid Analgesic Agents and Cancer Cell Biology

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