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OPRM1 A118G Polymorphisms and Its Role in Opioid Addiction: Implication on Severity and Treatment Approaches.

ABSTRACT: The epidemic of opioid addiction is shaping up as the most serious clinical issues of current times. Opioids have the greatest propensity to develop addiction after first exposure. Molecular, genetic variations, epigenetic alterations, and environmental factors are also implicated in the development of opioid addiction. Genetic and epigenetic variations in candidate genes have been identified for their associations with opioid addiction. OPRM1 nonsynonymous single nucleotide polymorphism rs1799971 (A118G) is the most prominent candidate due to its significant association with onset and treatment of opioid addiction. Marked inter-individual variability in response to available maintenance pharmacotherapies is the common feature observed in individuals with opioid addiction. Several therapies are only effective among subgroups of opioid individuals which indicate that ethnic, environmental factors and genetic polymorphism including rs1799971 may be responsible for the response to treatment. Pharmacogenetics has the potential to enhance our understanding around the underlying genetic, epigenetic and molecular mechanisms responsible for the heterogeneous response of maintenance pharmacotherapies in opioid addiction. A more detailed understanding of molecular, epigenetic and genetic variants especially the implication of OPRM1 A118G polymorphism in an individual may serve as the way forward to address the opioid epidemic. Personalized medicine, which involves developing targeted pharmacotherapies in accordance with individual genetic and epigenetic makeup, are required to develop safe and effective treatments for opioid addiction.

SUBMITTER: Taqi MM

PROVIDER: S-EPMC6885558 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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<i>OPRM1</i> A118G Polymorphisms and Its Role in Opioid Addiction: Implication on Severity and Treatment Approaches.

Taqi Malik Mumtaz MM Faisal Muhammad M Zaman Hadar H

Pharmacogenomics and personalized medicine 20191127

The epidemic of opioid addiction is shaping up as the most serious clinical issues of current times. Opioids have the greatest propensity to develop addiction after first exposure. Molecular, genetic variations, epigenetic alterations, and environmental factors are also implicated in the development of opioid addiction. Genetic and epigenetic variations in candidate genes have been identified for their associations with opioid addiction. <i>OPRM1</i> nonsynonymous single nucleotide polymorphism ...[more]

PMID: 31819591

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Project description:Mu-opioid receptors (MOPRs) are critically involved in the modulation of pain and analgesia, and represent a candidate mechanism for the development of biomarkers of pain conditions and their responses to treatment. To further understand the human implications of genetic variation within the opioid system in pain and opioid-mediated placebo responses, we investigated the association between the functional single-nucleotide polymorphism (SNP) in the μ-opioid receptor gene (OPRM1), A118G, and psychophysical responses, personality traits, and neurotransmitter systems (dopamine (DA), opioid) related to pain and placebo analgesia. OPRM1 G carriers, compared with AA homozygotes, showed an overall reduction of baseline μ-opioid receptor availability in regions implicated in pain and affective regulation. In response to a sustained painful stimulus, we found no effect of A118G on pain-induced endogenous opioid release. Instead, AA homozygotes showed a blunted DA response in the nucleus accumbens (NAc) in response to the pain challenge. After placebo administration, G carriers showed more pronounced mood disturbances and lower placebo-induced μ-opioid system activation in the anterior insula (aINS), the amygdala (AMY), the NAc, the thalamus (THA), and the brainstem, as well as lower levels of DA D2/3 activation in the NAc. At a trait level, G carriers reported higher NEO-Neuroticism scores; a personality trait previously associated with increased pain and lower placebo responses, which were negatively correlated with baseline μ-opioid receptor availability in the aINS and subgenual anterior cingulate cortex (sgACC). Our results demonstrate that the A118G OPRM1 polymorphism contributes to interindividual variations in the function of neurotransmitters responsive to pain (endogenous opioid and dopamine), as well as their regulation through cognitive-emotional influences in the context of therapeutic expectations, the so-called placebo effect. These effects are relevant to human vulnerability to disease processes where these neurotransmitters have a role, such as persistent pain, mood, and substance use disorders, and responses to their treatments.

Dataset Information

OPRM1 A118G Polymorphisms and Its Role in Opioid Addiction: Implication on Severity and Treatment Approaches.

Publications

<i>OPRM1</i> A118G Polymorphisms and Its Role in Opioid Addiction: Implication on Severity and Treatment Approaches.

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