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https://www.readbyqxmd.com/read/28805974/effect-of-single-nucleotide-polymorphisms-in-adh1b-adh4-adh1c-oprm1-drd2-bdnf-and-aldh2-genes-on-alcohol-dependence-in-a-caucasian-population
#1
Martha-Spyridoula Katsarou, Konstantinos Karakonstantis, Nikolaos Demertzis, Emmanouil Vourakis, Aspasia Skarpathioti, Aleksandr E Nosyrev, Aristidis Tsatsakis, Theodoris Kalogridis, Nikolaos Drakoulis
Alcohol is a frequently used addictive substance worldwide. Aim of this study is to determine the frequency distribution of SNPs within ADH1B, ADH4, ADH1C, ALDH2, BDNF, OPRM1, and DRD2 genes in a southeastern European Caucasian population from Greece. For this purpose samples of 1276 volunteers were analyzed after deidentification and anonymization. The allele distribution of the examined polymorphisms in the present Greek population cohort was as follows: rs1229984 (ADH1B): GG(wt) = 64.14%, GA = 29.86%, AA = 4...
August 2017: Pharmacology Research & Perspectives
https://www.readbyqxmd.com/read/28780411/increased-ethanol-drinking-in-humanized-mice-expressing-the-mu-opioid-receptor-a118g-polymorphism-are-mediated-through-sex-specific-mechanisms
#2
Angela N Henderson-Redmond, Tammy E Lowe, Xi B Tian, Daniel J Morgan
The A118G single nucleotide polymorphism (SNP) of the mu-opioid receptor gene (Oprm1) has been implicated in mediating the rewarding effects of alcohol. Clinical and preclinical studies suggest that the G allele may confer a genetic vulnerability to alcohol dependence, though it remains unknown whether these effects are sex-specific. We used male and female mice homozygous for the "humanized" 118AA or 118GG alleles to determine whether the A118G SNP potentiates ethanol consumption in a sex-specific manner in both the two-bottle choice and drinking-in-the-dark (DID) paradigms...
August 2, 2017: Brain Research Bulletin
https://www.readbyqxmd.com/read/28745577/advanced-cancer-pain-the-search-for-genetic-factors-correlated-with-interindividual-variability-in-opioid-requirement
#3
Maja Matic, Joost Lm Jongen, Laure Elens, Saskia N de Wildt, Dick Tibboel, Peter Ae Sillevis Smitt, Ron Hn van Schaik
AIM: To assess association between genetic variants and opioid requirement in cancer patients. MATERIALS & METHODS: A prospective observational trial of 243 advanced cancer patients with inadequate analgesia treated by the palliative care team was analyzed for ABCB1, ARRB2, COMT, GCH1, IL1RN, KCNJ6, OPRM1, RHBDF2, SCN9A and Stat6 polymorphisms. RESULTS: For patients carrying OPRM1 118AG/GG and COMT 472GG (Val158Val) or these genotypes alone, a significant higher median percentage dose increase was observed (95...
August 2017: Pharmacogenomics
https://www.readbyqxmd.com/read/28740224/depression-and-catechol-o-methyltransferase-comt-genetic-variants-are-associated-with-pain-in-parkinson-s-disease
#4
Chin-Hsien Lin, K Ray Chaudhuri, Jun-Yu Fan, Chia-I Ko, Alexandra Rizos, Chia-Wen Chang, Han-I Lin, Yih-Ru Wu
Pain is a distressing symptom of Parkinson disease (PD). We aim to determine whether the genetic variants of chronic pain-related genes contribute to pain in PD patients. We included 418 PD patients and evaluated pain severity on King's PD pain scale. We genotyped rs6267, rs6269, rs4633, rs4818 and rs4680 of COMT, rs6746030 of SCN9A, and rs1799971 of OPRM1. In total, 193 participants (46.2%) experienced pain. Compared to pain-free PD patients, PD patients with pain had an earlier age of onset, longer disease duration, and higher depression and motor severity (P < 0...
July 24, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28699646/review-of-opioid-pharmacogenetics-and-considerations-for-pain-management
#5
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
#6
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
#7
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
#8
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
#9
Jagadeesh Gandla, Santosh Kumar Lomada, Jianning Lu, Rohini Kuner, Kiran Kumar Bali
Pathophysiological mechanisms underlying pain associated with cancer are poorly understood. microRNAs (miRNAs) are a class of noncoding RNAs with emerging functional importance in chronic pain. In a genome-wide screen for miRNAs 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 miRNA. Despite these functional insights and therapeutic potential for miR-34c-5p, its molecular mechanism of action in peripheral sensory neurons remains unknown...
September 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
#10
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
#11
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
#12
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
#13
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
#14
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
#15
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 chronic cancer pain as well as high-dose opioid use lead to mu-opioid receptor downregulation. In this study we explore downregulation of the mu-opioid receptor gene (OPRM1), as a mechanism for 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 27, 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
#16
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
#17
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
#18
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
#19
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
#20
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
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