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https://www.readbyqxmd.com/read/28699646/review-of-opioid-pharmacogenetics-and-considerations-for-pain-management
#1
Aniwaa Owusu Obeng, Issam Hamadeh, Michael Smith
Opioid analgesics are the standards of care for the treatment of moderate to severe nociceptive pain, particularly in the setting of cancer and surgery. Their analgesic properties mainly emanate from stimulation of the μ receptors, which are encoded by the OPRM1 gene. Hepatic metabolism represents the major route of elimination, which, for some opioids, namely codeine and tramadol, is necessary for their bioactivation into more potent analgesics. The highly polymorphic nature of the genes coding for phase I and phase II enzymes (pharmacokinetics genes) that are involved in the metabolism and bioactivation of opioids suggests a potential interindividual variation in their disposition and, most likely, response...
July 12, 2017: Pharmacotherapy
https://www.readbyqxmd.com/read/28692418/contribution-of-genetic-polymorphisms-and-haplotypes-in-drd2-bdnf-and-opioid-receptors-to-heroin-dependence-and-endophenotypes-among-the-han-chinese
#2
Xuan Gao, Youxin Wang, Minglin Lang, Li Yuan, Albert Stuart Reece, Wei Wang
Heroin and drug dependence are major contributors to global health burden worldwide, but their underlying mechanisms remain elusive and may vary from population to population. Reward- and memory-related candidate genes dopamine D2 receptor (DRD2) and brain-derived neurotrophic factor (BDNF), as well as the opioid receptor genes (OPRM1, OPRD1, and OPRK1), have been implicated in drug dependence, but relatively little is known on their contributions to heroin dependence in populations worldwide. Hence, we evaluated the contributions of the above five candidate genes in heroin dependence and several important related endophenotypes (the onset age of heroin use and subjective response to first heroin use), at single single-nucleotide polymorphism as well as haplotype levels, in a Han Chinese population sample...
July 2017: Omics: a Journal of Integrative Biology
https://www.readbyqxmd.com/read/28650467/genome-wide-loss-of-function-genetic-screening-identifies-opioid-receptor-%C3%AE-1-as-a-key-regulator-of-l-asparaginase-resistance-in-pediatric-acute-lymphoblastic-leukemia
#3
S M Kang, J L Rosales, V Meier-Stephenson, S Kim, K Y Lee, A Narendran
L-asparaginase is a critical chemotherapeutic agent for acute lymphoblastic leukemia (ALL). It hydrolyzes plasma asparagine into aspartate and NH3, causing asparagine deficit and inhibition of protein synthesis and eventually, leukemic cell death. However, patient relapse often occurs due to development of resistance. The molecular mechanism by which ALL cells acquire resistance to L-asparaginase is unknown. Therefore, we sought to identify genes that are involved in L-asparaginase resistance in primary leukemic cells...
June 26, 2017: Oncogene
https://www.readbyqxmd.com/read/28637770/analgesia-and-opioids-a-pharmacogenetics-shortlist-for-implementation-in-clinical-practice
#4
REVIEW
Maja Matic, Saskia N de Wildt, Dick Tibboel, Ron H N van Schaik
BACKGROUND: The use of opioids to alleviate pain is complicated by the risk of severe adverse events and the large variability in dose requirements. Pharmacogenetics (PGx) could possibly be used to tailor pain medication based on an individual's genetic background. Many potential genetic markers have been described, and the importance of genetic predisposition in opioid efficacy and toxicity has been demonstrated in knockout mouse models and human twin studies. Such predictors are especially of value for neonates and young children, in whom the assessment of efficacy or side effects is complicated by the inability of the patient to communicate this properly...
July 2017: Clinical Chemistry
https://www.readbyqxmd.com/read/28614186/mir-34c-5p-functions-as-pronociceptive-microrna-in-cancer-pain-by-targeting-cav2-3-containing-calcium-channels
#5
Jagadeesh Gandla, Santosh Kumar Lomada, Jianning Lu, Rohini Kuner, Kiran Kumar Bali
Pathophysiological mechanisms underlying pain associated with cancer are poorly understood. microRNAs are a class of non-coding RNAs with emerging functional importance in chronic pain. In a genome-wide screen for microRNAs regulated in dorsal root ganglia (DRG) neurons in a mouse model of bone metastatic pain, we identified miR-34c-5p as a functionally important pronociceptive microRNA. Despite these functional insights and therapeutic potential for miR-34c-5p, its molecular mechanism of action in peripheral sensory neurons remains unknown...
June 9, 2017: Pain
https://www.readbyqxmd.com/read/28591085/influence-of-oprm1-polymorphism-on-post-operative-pain-after-intrathecal-morphine-administration-in-italian-patients-undergoing-elective-cesarean-section
#6
Eleonora Pettini, Massimo Micaglio, Ubaldo Bitossi, Angelo Raffaele De Gaudio, Duccio Rossi Degl'Innocenti, Lorenzo Tofani, Vittorio Limatola, Chiara Adembri, Alessandro Di Filippo
OBJECTIVES: the aim of this prospective observational study was to evaluate the influence of OPRM1 polymorphism on the analgesic efficacy (including VAS scores and requirement for rescue analgesia) of a standard dose of intrathecal morphine METHODS:: an Italian cohort of 63 parturients, scheduled for elective cesarean section at a tertiary University Hospital, received a spinal anesthesia with hyperbaric bupivacaine and morphine 100 mcg. For the first 48 hours in the post-operative period the patients received acetaminophen 1 g IV q6hr...
June 6, 2017: Clinical Journal of Pain
https://www.readbyqxmd.com/read/28548579/genetic-variation-of-the-mu-opioid-receptor-oprm1-and-dopamine-d2-receptor-drd2-is-related-to-smoking-differences-in-patients-with-schizophrenia-but-not-bipolar-disorder
#7
Mika Hirasawa-Fujita, Michael J Bly, Vicki L Ellingrod, Gregory W Dalack, Edward F Domino
It is not known why mentally ill persons smoke excessively. Inasmuch as endogenous opioid and dopaminergic systems are involved in smoking reinforcement, it is important to study mu opioid receptor (OPRM1) A118G (rs1799971), dopamine D2 receptor (DRD2) Taq1A (rs1800497) genotypes, and sex differences among patients with schizophrenia or bipolar disorder. Smokers and nonsmokers with schizophrenia (n=177) and bipolar disorder (n=113) were recruited and genotyped. They were classified into three groups: current smoker, former smoker, and never smoker by tobacco smoking status self-report...
December 0: Clinical Schizophrenia & related Psychoses
https://www.readbyqxmd.com/read/28533693/dna-methylation-at-the-mu-1-opioid-receptor-gene-oprm1-promoter-predicts-preoperative-acute-and-chronic-postsurgical-pain-after-spine-fusion
#8
Vidya Chidambaran, Xue Zhang, Lisa J Martin, Lili Ding, Matthew T Weirauch, Kristie Geisler, Bobbie L Stubbeman, Senthilkumar Sadhasivam, Hong Ji
INTRODUCTION: The perioperative pain experience shows great interindividual variability and is difficult to predict. The mu-1 opioid receptor gene (OPRM1) is known to play an important role in opioid-pain pathways. Since deoxyribonucleic acid (DNA) methylation is a potent repressor of gene expression, DNA methylation was evaluated at the OPRM1 promoter, as a predictor of preoperative, acute, and chronic postsurgical pain (CPSP). METHODS: A prospective observational cohort study was conducted in 133 adolescents with idiopathic scoliosis undergoing spine fusion under standard protocols...
2017: Pharmacogenomics and Personalized Medicine
https://www.readbyqxmd.com/read/28511993/the-expression-of-opioid-genes-in-non-classical-reward-areas-depends-on-early-life-conditions-and-ethanol-intake
#9
Linnea Granholm, Aniruddah Todkar, Sofia Bergman, Kent Nilsson, Erika Comasco, Ingrid Nylander
The young brain is highly sensitive to environmental influences that can cause long-term changes in neuronal function, possibly through altered gene expression. The endogenous opioid system continues to mature after birth and because of its involvement in reward, an inadequate maturation of this system could lead to enhanced susceptibility for alcohol use disorder. Recent studies show that the classical reward areas nucleus accumbens and ventral tegmental area are less affected by early life stress whereas endogenous opioids in non-classical areas, e...
May 13, 2017: Brain Research
https://www.readbyqxmd.com/read/28471875/genetic-predictors-of-recovery-in-low-back-and-lumbar-radicular-pain
#10
Siri Bjorland, Cecilie Røe, Aurora Moen, Elina Schistad, Aqsa Mahmood, Johannes Gjerstad
Previous data suggest that persistent back pain may be associated with genetic variability. In this study, we assessed the correlation between 8 genetic polymorphisms (VDR, COL11, MMP1, MMP9, IL-1α, IL-1RN, OPRM1, COMT) and pain recovery in patients with low back pain (LBP) and lumbar radicular pain (LRP). In total, 296 patients with LBP or LRP were followed for 5 years. The patients underwent standardized clinical examination and completed pain and function questionnaires. Univariate linear regression associations with P values <0...
April 27, 2017: Pain
https://www.readbyqxmd.com/read/28456745/oprm1-methylation-contributes-to-opioid-tolerance-in-cancer-patients
#11
Chi T Viet, Dongmin Dang, Bradley E Aouizerat, Christine Miaskowski, Yi Ye, Dan T Viet, Kentaro Ono, Brian L Schmidt
Cancer patients in pain require high doses of opioids and quickly become opioid-tolerant. Previous studies have shown that both chronic cancer pain and high dose opioid use lead to mu-opioid receptor down-regulation. In this study we explore down-regulation of OPRM1, the mu-opioid receptor gene, as a mechanism f,or opioid tolerance in the setting of opioid use for cancer pain. We demonstrate in a cohort of 84 cancer patients that high dose opioid use correlates with OPRM1 hypermethylation in peripheral leukocytes of these patients...
April 26, 2017: Journal of Pain: Official Journal of the American Pain Society
https://www.readbyqxmd.com/read/28409564/predictors-of-naltrexone-response-in-a-randomized-trial-reward-related-brain-activation-oprm1-genotype-and-smoking-status
#12
Joseph P Schacht, Patrick K Randall, Patricia K Latham, Konstantin E Voronin, Sarah W Book, Hugh Myrick, Raymond F Anton
Naltrexone reduces drinking among individuals with alcohol use disorders (AUDs), but it is not effective for everyone. Variability in its effects on reward-related brain activation, genetic variation, and/or cigarette smoking may account for this mixed response profile. This randomized clinical trial tested the effects of naltrexone on drinking and alcohol cue-elicited brain activation, evaluated whether OPRM1 A118G genotype or smoking moderated these effects, and explored whether the effects of medication on cue-elicited activation predicted subsequent drinking...
April 14, 2017: Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology
https://www.readbyqxmd.com/read/28398354/global-genetic-variation-of-select-opiate-metabolism-genes-in-self-reported-healthy-individuals
#13
F R Wendt, G Pathak, A Sajantila, R Chakraborty, B Budowle
CYP2D6 is a key pharmacogene encoding an enzyme impacting poor, intermediate, extensive and ultrarapid phase I metabolism of many marketed drugs. The pharmacogenetics of opiate drug metabolism is particularly interesting due to the relatively high incidence of addiction and overdose. Recently, trans-acting opiate metabolism and analgesic response enzymes (UGT2B7, ABCB1, OPRM1 and COMT) have been incorporated into pharmacogenetic studies to generate more comprehensive metabolic profiles of patients. With use of massively parallel sequencing, it is possible to identify additional polymorphisms that fine tune, or redefine, previous pharmacogenetic findings, which typically rely on targeted approaches...
April 11, 2017: Pharmacogenomics Journal
https://www.readbyqxmd.com/read/28379874/effects-of-single-nucleotide-polymorphisms-on-surgical-and-post-surgical-opioid-requirements-a-systematic-review-and-meta-analysis
#14
Siu-Wai Choi, David M H Lam, Stanley S C Wong, Haydn H C Shiu, Amy X M Wang, Chi-Wai Cheung
OBJECTIVES: There is great heterogeneity in the way individuals respond to medications. Inherited differences, such as Single Nucleotide Polymorphisms (SNP), can influence the efficacy and toxicity of drugs. This meta-analysis aims to collate data from studies investigating the effect of SNPs on post-operative and/or intra-operative opioid requirements. METHODS: This meta-analysis was conducted following PRISMA guidelines. Eligibility criteria for studies in this meta-analysis were reporting amount of post-operative and/or intra-operative opioid used as the primary outcome and genotyping patients for SNPs in one of the following genes; OPRM1, CYP2D6, CYP3A4, CYP3A5, COMT, UGT2B7 or ABCB1...
April 4, 2017: Clinical Journal of Pain
https://www.readbyqxmd.com/read/28376280/independent-and-interactive-effects-of-oprm1-and-dat1-polymorphisms-on-alcohol-consumption-and-subjective-responses-in-social-drinkers
#15
Elise M Weerts, Gary S Wand, Brion Maher, Xiaoqiang Xu, Mary Ann Stephens, Xiaoju Yang, Mary E McCaul
BACKGROUND: The current study examined independent and interactive effects of polymorphisms of the mu opioid receptor gene (OPRM1, A118G) and variable number tandem repeats of the dopamine transporter gene (DAT1, SLC6A3) on alcohol consumption and subjective responses to alcohol in 127 young, healthy, social drinkers. METHODS: Participants completed an in-person assessment, which included self-reported alcohol drinking patterns and blood sampling for DNA, and in a second visit, a cumulative alcohol dosing procedure with subjective ratings across multiple time points and breath alcohol contents (0...
June 2017: Alcoholism, Clinical and Experimental Research
https://www.readbyqxmd.com/read/28349993/cannabinoid-receptor-type-1-and-mu-opioid-receptor-polymorphisms-are-associated-with-cyclic-vomiting-syndrome
#16
Andrzej Wasilewski, Urszula Lewandowska, Paula Mosinska, Cezary Watala, Martin Storr, Jakub Fichna, Thangam Venkatesan
OBJECTIVES: Cyclic vomiting syndrome (CVS) is a disorder defined by recurrent, unexplained episodes of severe nausea and vomiting. Our aim was to investigate whether CVS and pathophysiological mechanisms underlying this condition are associated with selected variations in genes encoding the components of the endogenous cannabinoid and opioid systems. METHODS: This case-control study included 65 patients with CVS-16 male and 49 female, and 1,092 healthy controls-525 male and 567 female from the 1000 Genomes Project...
June 2017: American Journal of Gastroenterology
https://www.readbyqxmd.com/read/28346387/oprm1-c-118a-g-polymorphism-and-duration-of-morphine-treatment-associated-with-morphine-doses-and-quality-of-life-in-palliative-cancer-pain-settings
#17
Aline Hajj, Lucine Halepian, Nada El Osta, Georges Chahine, Joseph Kattan, Lydia Rabbaa Khabbaz
Despite increased attention on assessment and management, pain remains the most persistent symptom in patients with cancer, in particular in end-of-life settings, with detrimental impact on their quality-of-life (QOL). We conducted this study to evaluate the added value of determining some genetic and non-genetic factors to optimize cancer pain treatment. Eighty-nine patients were included in the study for the evaluation of palliative cancer pain management. The regression analysis showed that age, OPRM1 single nucleotide polymorphism (SNP), as well as the duration of morphine treatment were significantly associated with morphine doses at 24 h (given by infusion pump; p = 0...
March 27, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28343361/genetic-dissociation-of-morphine-analgesia-from-hyperalgesia-in-mice
#18
Gina F Marrone, Valerie Le Rouzic, Andras Varadi, Jin Xu, Anjali M Rajadhyaksha, Susruta Majumdar, Ying-Xian Pan, Gavril W Pasternak
RATIONALE: Morphine is the prototypic mu opioid, producing its analgesic actions through traditional 7 transmembrane domain (7TM) G-protein-coupled receptors generated by the mu opioid receptor gene (Oprm1). However, the Oprm1 gene undergoes extensive alternative splicing to yield three structurally distinct sets of splice variants. In addition to the full-length 7TM receptors, it produces a set of truncated variants comprised of only 6 transmembrane domains (6TM). OBJECTIVES: This study explored the relative contributions of 7TM and 6TM variants in a range of morphine actions...
March 25, 2017: Psychopharmacology
https://www.readbyqxmd.com/read/28339912/pharmacogenomics-and-patient-treatment-parameters-to-opioid-treatment-in-chronic-pain-a-focus-on-morphine-oxycodone-tramadol-and-fentanyl
#19
Renae A Lloyd, Elizabeth Hotham, Catherine Hall, Marie Williams, Vijayaprakash Suppiah
Objective. : Opioids are one of the most commonly prescribed medicines for chronic pain. However, their use for chronic pain has been controversial. The objective of this literature review was to identify the role of genetic polymorphisms on patient treatment parameters (opioid dose requirements, response, and adverse effects) for opioids used in malignant and nonmalignant chronic pain. The opioids that this review focuses on are codeine, morphine, oxycodone, tramadol, and fentanyl...
February 24, 2017: Pain Medicine: the Official Journal of the American Academy of Pain Medicine
https://www.readbyqxmd.com/read/28320034/variations-in-infant-cyp2b6-genotype-associated-with-the-need-for-pharmacological-treatment-for-neonatal-abstinence-syndrome-in-infants-of-methadone-maintained-opioid-dependent-mothers
#20
Helen Mactier, Poppy McLaughlin, Cheryl Gillis, Michael David Osselton
Background Neonatal abstinence syndrome (NAS) in infants of methadone-maintained opioid-dependent (MMOD) mothers cannot be predicted in individual cases. We investigated whether variation in infant genotype is associated with severity of NAS. Methods This is a pilot observational cohort study of 21 MMOD mothers and their newborns. Infant buccal swabs were obtained soon after delivery, together with a maternal blood sample for the determination of maternal plasma methadone concentration. Genomic variation in five opioid-related genes (ABCB1, COMT, CYP2B6, CYP2D6, and OPRM1) was ascertained from infant buccal swabs and related to need for pharmacological treatment of NAS...
July 2017: American Journal of Perinatology
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