Pharmacogenetics of OPRM1.
paper
Cited
Public
- Authors
- Crist, Richard C; Berrettini, Wade H
- Year
- 2014
- Journal
- Pharmacology, biochemistry, and behavior
- PMID
- 24201053
- DOI
- 10.1016/j.pbb.2013.10.018
- PMCID
- PMC4010567
Pharmacogenetic research has the potential to explain the variation in treatment efficacy within patient populations. Understanding the interaction between genetic variation and medications may provide a method for matching patients to the most effective therapeutic options and improving overall patient outcomes. The OPRM1 gene has been a target of interest in a large number of pharmacogenetic studies due to its genetic and structural variation, as well as the role of opioid receptors in a variety of disorders. The mu-opioid receptor (MOR), encoded by OPRM1, naturally regulates the analgesic response to pain and also controls the rewarding effects of many drugs of abuse, including opioids, nicotine, and alcohol. Genetic variants in OPRM1, particularly the non-synonymous polymorphism A118G, have been repeatedly associated with the efficacy of treatments for pain and various types of dependence. This review focuses on the current understanding of the pharmacogenetic impact of OPRM1, primarily with regard to the treatment of pain and addiction.
Diagram of the OPRM1 gene with the locations of genetic variants associated with pharmacogenetic effects in analgesia (bolded) or addiction treatment (underlined). Gray boxes indicate exons and boxes with diagonal lines indicate untranslated regions. SNP and exon locations taken from the February 2009 build of the human genome in UCSC Genome Browser (www.genome.ucsc.edu)
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| Name | Type |
|---|---|
| A118G A/A genotype local | variant |
| A118G G allele local | variant |
| A118G SNP | variant |
| A118G variant local | variant |
| A/A genotype local | cohort |
| A/A genotype of A118G local | variant |
| abstinence | phenotype |
| acetaminophen | drug |
| addiction | phenotype |
| addiction treatment local | phenotype |
| addictive potential | phenotype |
| adolescents | cohort |
| Adult Caucasians local | cohort |
| Adverse medication response local | phenotype |
| African American case-control cohort local | cohort |
| African-Americans | cohort |
| alcohol | phenotype |
| alcohol dependence | phenotype |
| alcoholism | phenotype |
| Alcohol Use Disorder | phenotype |
| Alfentanil | drug |
| analgesic dose requirement local | phenotype |
| analgesic response | phenotype |
| Asian | cohort |
| aspirin | drug |
| aversion | phenotype |
| brain tissue | anatomy |
| British cohort local | cohort |
| buprenorphine | drug |
| Buprenorphine patients local | cohort |
| bupropion | drug |
| cAMP | drug |
| cancer | phenotype |
| cancer patients receiving opioids local | cohort |
| cardiovascular disease | phenotype |
| CA repeat intron1 local | variant |
| central side effects of morphine local | phenotype |
| cerebral blood flow | phenotype |
| Chemotherapeutics local | drug |
| Chinese | cohort |
| chronic opioid use | phenotype |
| codeine | drug |
| COMT | gene |
| constipation | phenotype |
| craving | phenotype |
| cytisine local | drug |
| DAMGO | drug |
| DAT1 VNTR | variant |
| DAT1 VNTR 9-copy local | variant |
| Decreased pupillary constriction local | phenotype |
| deltorphin local | drug |
| diabetic foot ulcer pain local | phenotype |
| dopamine | drug |
| dopamine release | drug |
| drinking | phenotype |
| drowsiness | phenotype |
| dynorphin | drug |
| dysphoria | phenotype |
| endogenous opioids | drug |
| endomorphins local | drug |
| endorphin | drug |
| enkephalin | drug |
| euphoria | phenotype |
| Euphoric effects of alcohol | phenotype |
| European ancestry | cohort |
| European population | cohort |
| Europeans | cohort |
| fentanyl | drug |
| fibromyalgia pain local | phenotype |
| frequency of alcohol use | phenotype |
| genetic variants | cohort |
| Gi/G0 proteins local | drug |
| hallucinations | phenotype |
| heavy drinking | phenotype |
| herniated disc pain local | phenotype |
| Higher plasma methadone level local | phenotype |
| hydrocodone | drug |
| ibuprofen local | drug |
| Indian cohort local | cohort |
| Indian population | cohort |
| insomnia | phenotype |
| ischemic pain local | phenotype |
| Japanese | cohort |
| KOR | drug |
| Koreans | cohort |
| Lerman et al. trial cohort local | cohort |
| Levomethadone local | drug |
| low abuse potential local | phenotype |
| Malaysian cohort local | cohort |
| Malaysians local | cohort |
| Male social drinkers local | cohort |
| Mesocorticolimbic regions local | anatomy |
| Meso-limbic system local | anatomy |
| Methadone | drug |
| Methadone maintenance patients local | cohort |
| Methadone maintenance therapy local | cohort |
| migraine pain local | phenotype |
| MOR | drug |
| morphine | drug |
| Morphine-6-glucoronide local | drug |
| morphine-6-glucuronide local | drug |
| mu opioid receptor | drug |
| nalmefene | drug |
| naloxone | drug |
| naltrexone | drug |
| National Survey on Drug Use and Health | cohort |
| nausea | phenotype |
| negative reinforcement | phenotype |
| nicotine | drug |
| nicotine addiction | phenotype |
| nicotine dependence | phenotype |
| nicotine nasal spray | drug |
| nicotine replacement therapy | drug |
| nicotinic acetylcholine receptor | drug |
| non-opioid analgesics local | drug |
| norepinephrine | drug |
| NRT | drug |
| NSAIDs | drug |
| opioid | drug |
| opioid dependence | phenotype |
| Opioid medications local | drug |
| Opioid positive urine drug screen local | phenotype |
| Oprd1 | cohort |
| OPRK1 | cohort |
| OPRM1 | cohort |
| OPRM1 3′ UTR length variation local | variant |
| OPRM1 A118G | cohort |
| OPRM1 A118G A/A genotype local | variant |
| OPRM1 A118G G allele local | variant |
| OPRM1 G/G genotype local | variant |
| OPRM1 splice variant | variant |
| OPRM1 structural variation local | variant |
| Optimal methadone dose local | phenotype |
| oral NRT local | drug |
| outcome | phenotype |
| oxycodone | drug |
| pain | phenotype |
| pain sensations local | phenotype |
| persistent widespread pain local | phenotype |
| pharmacological outcome local | phenotype |
| positive reinforcement | phenotype |
| pressure pain threshold | phenotype |
| proopiomelanocortin precursor local | drug |
| pruritus | phenotype |
| Rapid detoxification local | phenotype |
| Reduced ability to focus local | phenotype |
| Reduced analgesia local | phenotype |
| Reduced libido local | phenotype |
| relapse | phenotype |
| relapse rates | phenotype |
| respiratory depression | phenotype |
| reward from nicotine local | phenotype |
| rewarding effects | phenotype |
| rs10485057 | variant |
| rs1074287 | variant |
| rs1799971 | variant |
| rs1799972 | variant |
| rs2075572 | variant |
| rs2236861 | variant |
| rs4680 | variant |
| rs495491 | variant |
| rs499796 local | variant |
| rs510769 | variant |
| rs548646 local | variant |
| rs563649 | variant |
| rs6091485 local | variant |
| rs634479 local | variant |
| rs648893 local | variant |
| rs679987 local | variant |
| rs9384179 local | variant |
| rs9479757 local | variant |
| rs9479757/rs2075572/rs10485057 haplotype local | variant |
| SLC6A3 | gene |
| Small-cell lung carcinoma local | phenotype |
| smoking | phenotype |
| smoking cessation | phenotype |
| smoking initiation | phenotype |
| striatum | anatomy |
| stroke | phenotype |
| sufentanil | drug |
| Suppressed HPA axis activation local | phenotype |
| Taiwanese cohort local | cohort |
| thermal pain local | phenotype |
| tobacco use | phenotype |
| Tramadol local | drug |
| transdermal patch | drug |
| treatment efficacy | phenotype |
| urge to drink | phenotype |
| varenicline | drug |
| ventral striatum | anatomy |
| vomiting | phenotype |
| withdrawal | phenotype |
| β-endorphin | drug |
| δ-opioid receptor local | drug |
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