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opioid genetics

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https://www.readbyqxmd.com/read/28801372/multi-variant-genetic-panel-for-genetic-risk-of-opioid-addiction
#1
Keri Donaldson, Laurence Demers, Kirk Taylor, Joe Lopez, Sherman Chang
Over 116 million people worldwide have chronic pain and prescription dependence. In the US, opioids account for the majority of overdose deaths, and in 2014, almost 2 million Americans abused or were dependent on prescription opioids. Genetic factors may play a key role in opioid prescription addiction. Herein, we describe genetic variations between opioid addicted and non-addicted populations and derive a predictive model determining risk of opioid addiction. This case cohort study compares the frequency of 16 single nucleotide polymorphisms involved in the brain reward pathways in patients with and without opioid addiction...
August 2017: Annals of Clinical and Laboratory Science
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/28770976/non-steroidal-anti-inflammatory-drugs-nsaids-for-chronic-non-cancer-pain-in-children-and-adolescents
#3
REVIEW
Christopher Eccleston, Tess E Cooper, Emma Fisher, Brian Anderson, Nick Mr Wilkinson
BACKGROUND: Pain is a common feature of childhood and adolescence around the world, and for many young people, that pain is chronic. The World Health Organization guidelines for pharmacological treatments for children's persisting pain acknowledge that pain in children is a major public health concern of high significance in most parts of the world. While in the past pain was largely dismissed and was frequently left untreated, views on children's pain have changed over time, and relief of pain is now seen as important...
August 2, 2017: Cochrane Database of Systematic Reviews
https://www.readbyqxmd.com/read/28768313/treatment-of-hailey-hailey-disease-with-low-dose-naltrexone
#4
Lauren N Albers, Jack L Arbiser, Ron J Feldman
Importance: Hailey-Hailey disease is a severe genetic blistering disease of intertriginous skin locations that can lead to poor quality of life and increased morbidities. Multiple therapies are available with inconsistent outcomes and potentially severe adverse effects. Objective: To determine whether low-dose naltrexone is an effective treatment for Hailey-Hailey disease. Design, Setting, and Participants: This study was a case series performed at a dermatology outpatient clinic of 3 patients with severe Hailey-Hailey disease recalcitrant to at least 4 therapies...
August 2, 2017: JAMA Dermatology
https://www.readbyqxmd.com/read/28745932/genetic-deletion-of-microglial-panx1-attenuates-morphine-withdrawal-but-not-analgesic-tolerance-or-hyperalgesia-in-mice
#5
Nicole E Burma, Heather Leduc-Pessah, Tuan Trang
Opioids are among the most powerful analgesics for managing pain, yet their repeated use can lead to the development of severe adverse effects. In a recent study, we identified the microglial pannexin-1 channel (Panx1) as a critical substrate for opioid withdrawal. Here, we investigated whether microglial Panx1 contributes to opioid-induced hyperalgesia (OIH) and opioid analgesic tolerance using mice with a tamoxifen-inducible deletion of microglial Panx1. We determined that escalating doses of morphine resulted in thermal pain hypersensitivity in both Panx1-expressing and microglial Panx1-deficient mice...
July 26, 2017: Channels
https://www.readbyqxmd.com/read/28745577/advanced-cancer-pain-the-search-for-genetic-factors-correlated-with-interindividual-variability-in-opioid-requirement
#6
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/28738753/genetic-predictors-of-celiac-disease-lactose-intolerance-and-vitamin-d-function-and-presence-of-peptide-morphins-in-urine-of-children-with-neurodevelopmental-disorders
#7
Katarina Bojović, Biljana Stanković, Nikola Kotur, Dijana Krstić-Milošević, Vladimir Gašić, Sonja Pavlović, Branka Zukić, Đurđica Ignjatović
Gastrointestinal disturbances, nutritional deficiencies, and food intolerances are frequently observed in children with neurodevelopmental disorders (NDD). To reveal possible association of celiac disease risk variants (HLA-DQ), lactose intolerance associated variant (LCT-13910C>T) as well as variant associated with vitamin D function (VDR FokI) with NDD, polymerase chain reaction-based methodology was used. Additionally, intestinal peptide permeability was estimated in NDD patients and healthy children by measuring the level of peptides in urine using high-performance liquid chromatography...
July 24, 2017: Nutritional Neuroscience
https://www.readbyqxmd.com/read/28734904/identifying-novel-members-of-the-wntless-interactome-through-genetic-and-candidate-gene-approaches
#8
Jessica Petko, Trevor Tranchina, Goral Patel, Robert Levenson, Stephanie Justice-Bitner
Wnt signaling is an important pathway that regulates several aspects of embryogenesis, stem cell maintenance, and neural connectivity. We have recently determined that opioids decrease Wnt secretion, presumably by inhibiting the recycling of the Wnt trafficking protein Wntless (Wls). This effect appears to be mediated by protein-protein interaction between Wls and the mu-opioid receptor (MOR), the primary cellular target of opioid drugs. The goal of this study was to identify novel protein interactors of Wls that are expressed in the brain and may also play a role in reward or addiction...
July 20, 2017: Brain Research Bulletin
https://www.readbyqxmd.com/read/28704923/production-of-cow-s-milk-free-from-beta-casein-a1-and-its-application-in-the-manufacturing-of-specialized-foods-for-early-infant-nutrition
#9
Miguel Á Duarte-Vázquez, Carlos García-Ugalde, Laura M Villegas-Gutiérrez, Blanca E García-Almendárez, Jorge L Rosado
Beta-casein (BC) is frequently expressed as BC A2 and BC A1 in cow's milk. Gastrointestinal digestion of BC A1 results in the release of the opioid peptide beta-casomorphin 7 (BCM7) which is less likely to occur from BC A2. This work was aimed to produce milk containing BC A2 with no BC A1 (BC A2 milk) using genetically selected CSN2 A2A2 Jersey cows. Additionally, we aimed to develop an infant formula (IF) suitable for healthy full-term infants during the first six months of life based on BC A2 milk. The concentration of BCM7 released from BC A2 IF, from commercially available IFs as well as from human milk and raw cow's milk was evaluated after simulated gastrointestinal digestion (SGID)...
July 12, 2017: Foods (Basel, Switzerland)
https://www.readbyqxmd.com/read/28704071/social-monogamy-in-nonhuman-primates-phylogeny-phenotype-and-physiology
#10
Jeffrey A French, Jon Cavanaugh, Aaryn C Mustoe, Sarah B Carp, Stephanie L Womack
Monogamy as a social system has been both a scientific puzzle and a sociocultural issue for decades. In this review, we examine social monogamy from a comparative perspective with a focus on primates, our closest genetic relatives. We break down monogamy into component elements, including pair-bonding and partner preference, mate guarding or jealousy, social attachment, and biparental care. Our survey of primates shows that not all features are present in species classified as socially monogamous, in the same way that human monogamous relationships may not include all elements-a perspective we refer to as "monogamy à la carte...
July 13, 2017: Journal of Sex Research
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
#11
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/28656735/an-analysis-of-genetic-association-in-opioid-dependence-susceptibility
#12
D Nagaya, Z Zahari, M Saleem, B H Yahaya, S C Tan, N M Yusoff
WHAT IS KNOWN: Drug addiction is a novelty-seeking personality trait that is associated with the candidate genes OPRD1 (opioid delta receptors), OPRK1 (opioid kappa receptors) and PDYN (prodynorphin). However, associations between single nucleotide polymorphisms (SNPs) rs1042114 (80G>T) of the OPRD1 gene, rs702764 (843 A>G) of the OPRK1 gene, and rs910080 (3' UTR _743T>C), rs1997794 (5' UTR -381A>G) and rs1022563 (3' UTR) of the PDYN gene and novelty seeking remain controversial as reported results have not been reproducible...
June 27, 2017: Journal of Clinical Pharmacy and Therapeutics
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
#13
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/28649993/kappa-opioid-receptor-activation-in-dopamine-neurons-disrupts-behavioral-inhibition
#14
Antony D Abraham, Harrison M Fontaine, Allisa J Song, Mackenzie M Andrews, Madison A Baird, Brigitte L Kieffer, Benjamin B Land, Charles Chavkin
The dynorphin/kappa opioid receptor (KOR) system has been previously implicated in the regulation of cognition, but the neural circuitry and molecular mechanisms underlying KOR-mediated cognitive disruption are unknown. Here, we used an operational test of cognition involving timing and behavioral inhibition and found that systemic KOR activation impairs performance of male and female C57BL/6 mice in the differential reinforcement of low response rates (DRL) task. Systemic KOR antagonism also blocked stress-induced disruptions of DRL performance...
June 26, 2017: Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology
https://www.readbyqxmd.com/read/28637770/analgesia-and-opioids-a-pharmacogenetics-shortlist-for-implementation-in-clinical-practice
#15
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/28632076/association-of-oprd1-gene-variants-with-opioid-dependence-in-addicted-male-individuals-undergoing-methadone-treatment-in-the-north-of-iran
#16
Alireza Sharafshah, Hedyeh Fazel, Ali Albonaim, Vahid Omarmeli, Sajjad Rezaei, Ebrahim Mirzajani, Farzam Ajamian, Parvaneh Keshavarz
Genetic association of rs678849 along with neuroimaging and biomarker phenotypes, parallel with the known involvements of the OPRD1 in drug abuse, provided additional support for targeting these receptors as potential therapeutic targets in both neurodegenerative diseases and neuropsychiactric disorders such as Alzheimer's disease. Samples were selected among 202 opium-addicted participants undergoing methadone treatment and 202 healthy controls. Genomic DNA of all subjects was extracted from whole blood samples through a Salting Out procedure...
March 1, 2017: Journal of Psychoactive Drugs
https://www.readbyqxmd.com/read/28622282/towards-a-neurobiological-understanding-of-alexithymia
#17
REVIEW
Nicolás Meza-Concha, Marcelo Arancibia, Felicia Salas, Rosa Behar, Germán Salas, Hernán Silva, Rocío Escobar
Although the specialized literature on the etiology of alexithymia is controversial, neurobiological research has shown relevant advances. The aim of this review is to analyze the available evidence regarding the neurophysiological bases of alexithymia. A comprehensive review of available articles from Medline/PubMed, EBSCO and SciELO was conducted. Previously, alexithymia was linked to a reduced interhemispheric brain connection. From a childhood traumatic perspective, the right prefrontal cortex and the default mode network would experience alterations, first hypermetabolic (dopaminergic and glutamatergic dysregulation) and then hypometabolic-dissociative (serotonergic and opioid dysregulation), resulting in a distorted interoceptive and emotional awareness...
May 29, 2017: Medwave
https://www.readbyqxmd.com/read/28621702/short-duration-physical-activity-prevents-the-development-of-activity-induced-hyperalgesia-through-opioid-and-serotoninergic-mechanisms
#18
Lucas V Lima, Josimari M DeSantana, Lynn A Rasmussen, Kathleen A Sluka
Regular physical activity prevents the development of chronic muscle pain through the modulation of central mechanisms that involve rostral ventromedial medulla (RVM). We tested if pharmacological blockade or genetic deletion of mu-opioid receptors in physically active mice modulates excitatory and inhibitory systems in the RVM in an activity-induced hyperalgesia model. We examined response frequency to mechanical stimulation of the paw, muscle withdrawal thresholds, and expression of phosphorylation of the NR1 subunit of the N-methyl-D-aspartate receptor (p-NR1) and serotonin transporter (SERT) in the RVM...
June 8, 2017: Pain
https://www.readbyqxmd.com/read/28619017/borderline-personality-disorder-and-childhood-trauma-exploring-the-affected-biological-systems-and-mechanisms
#19
Nadia Cattane, Roberta Rossi, Mariangela Lanfredi, Annamaria Cattaneo
BACKGROUND: According to several studies, the onset of the Borderline Personality Disorder (BPD) depends on the combination between genetic and environmental factors (GxE), in particular between biological vulnerabilities and the exposure to traumatic experiences during childhood. We have searched for studies reporting possible alterations in several biological processes and brain morphological features in relation to childhood trauma experiences and to BPD. We have also looked for epigenetic mechanisms as they could be mediators of the effects of childhood trauma in BPD vulnerability...
June 15, 2017: BMC Psychiatry
https://www.readbyqxmd.com/read/28594147/casein-kinase-1-epsilon-deletion-increases-mu-opioid-receptor-dependent-behaviors-and-binge-eating1
#20
L R Goldberg, S L Kirkpatrick, N Yazdani, K P Luttik, O A Lacki, R Keith Babbs, D F Jenkins, W Evan Johnson, C D Bryant
Genetic and pharmacological studies indicate that casein kinase 1 epsilon (Csnk1e) contributes to psychostimulant, opioid, and ethanol motivated behaviors. We previously used pharmacological inhibition to demonstrate that Csnk1e negatively regulates the locomotor stimulant properties of opioids and psychostimulants. Here, we tested the hypothesis that Csnk1e negatively regulates opioid and psychostimulant reward using genetic inhibition and the conditioned place preference assay in Csnk1e knockout mice. Similar to pharmacological inhibition, Csnk1e knockout mice showed enhanced opioid-induced locomotor activity with the mu opioid receptor agonist fentanyl (0...
June 8, 2017: Genes, Brain, and Behavior
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