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Application of pharmacogenetic tests

Emily C Williams, Jessica P Young, Carol E Achtmeyer, Christian S Hendershot
BACKGROUND: Efforts to identify genetic moderators of pharmacotherapy response have generated interest in clinical applications of pharmacogenetic tests in alcohol use disorder (AUD) treatment. To date, no research on providers' interest in using pharmacogenetic tests in the context of AUD treatment has been reported. We conducted qualitative interviews with primary care providers from 5 clinics in the Veterans Health Administration (VA) to assess their interest in using a hypothetical genetic test to inform treatment of AUD with pharmacotherapy...
November 2016: Journal of Substance Abuse Treatment
Linda Koshy, A L Anju, S Harikrishnan, V R Kutty, V T Jissa, Irin Kurikesu, Parvathy Jayachandran, A Jayakumaran Nair, A Gangaprasad, G M Nair, P R Sudhakaran
The extraction of genomic DNA is the crucial first step in large-scale epidemiological studies. Though there are many popular DNA isolation methods from human whole blood, only a few reports have compared their efficiencies using both end-point and real-time PCR assays. Genomic DNA was extracted from coronary artery disease patients using solution-based conventional protocols such as the phenol-chloroform/proteinase-K method and a non-phenolic non-enzymatic Rapid-Method, which were evaluated and compared vis-a-vis a commercially available silica column-based Blood DNA isolation kit...
September 29, 2016: Molecular Biology Reports
Nemanja Rancic, Viktorija Dragojevic-Simic, Neven Vavic, Aleksandra Kovacevic, Zoran Segrt, Natasa Djordjevic
Renal transplantation is the treatment of choice for the patients with end-stage renal failure. Genetic factors, among others, can influence variability in response to immunosuppressive drugs. Nowadays, due to restrictive health resources, the question arises whether routine pharmacogenetic analyses should be done in the renal transplant recipients or not. The aim of this literature review was to present the up-to-date information considering the economic feasibility of pharmacogenetic testing in patients subjected to renal transplantation...
2016: Frontiers in Public Health
Chiara Fabbri, Ladislav Hosak, Rainald Mössner, Ina Giegling, Laura Mandelli, Frank Bellivier, Stephan Claes, David A Collier, Alejo Corrales, Lynn E Delisi, Carla Gallo, Michael Gill, James L Kennedy, Marion Leboyer, Amanda Lisoway, Wolfgang Maier, Miguel Marquez, Isabelle Massat, Ole Mors, Pierandrea Muglia, Markus M Nöthen, Michael C O'Donovan, Jorge Ospina-Duque, Peter Propping, Yongyong Shi, David St Clair, Florence Thibaut, Sven Cichon, Julien Mendlewicz, Dan Rujescu, Alessandro Serretti
Major depressive disorder (MDD) is a heritable disease with a heavy personal and socio-economic burden. Antidepressants of different classes are prescribed to treat MDD, but reliable and reproducible markers of efficacy are not available for clinical use. Further complicating treatment, the diagnosis of MDD is not guided by objective criteria, resulting in the risk of under- or overtreatment. A number of markers of MDD and antidepressant response have been investigated at the genetic, epigenetic, gene expression and protein levels...
September 7, 2016: World Journal of Biological Psychiatry
Sarah Adelsperger, Cynthia A Prows, Melanie F Myers, Cassandra L Perry, Ariel Chandler, Ingrid A Holm, John A Lynch
Concerns about the ethical and social implications of genetics persist as more applications of genetic and genomic technology have become available. Pediatric testing for genetic influences on response to opioids like codeine is one area of application. We interviewed parents of children enrolled in a mixed-methods study following the communication of actual or hypothetical results for CYP2D6, which impacts opioid response. Forty-one parents of children naive to opioids and 42 parents of children previously exposed to opioids participated in qualitative interviews...
August 30, 2016: Health Communication
Filipp Filippovich Vasilyev, Diana Aleksandrovna Danilova, Vladimir Sergeevich Kaimonov, Yana Valerievna Chertovskih, Nadezda Romanovna Maksimova
Allele frequencies of single nucleotide polymorphisms (SNPs) are variable among different populations; therefore the study of SNPs in ethnic groups is important for establishing the clinical significance of the screening of these polymorphisms. The main goal of the research is to study the polymorphisms of CYP2C9, CYP2C19, VKORC1, and SLCO1B1 in Yakuts. Genomic DNA from 229 Yakut subjects were analyzed by real-time polymerase chain reaction (PCR) (SLCO1B1 +521T > C, VKORC1 -1639G>A, CYP2C19 +681G>A, +636G>A, CYP2C9 +430С>T, +1075A>C)...
May 2016: Research in Pharmaceutical Sciences
Marika Plöthner, Dana Ribbentrop, Jan-Phillipp Hartman, Martin Frank
BACKGROUND: The use of targeted therapies has recently increased. Pharmacogenetic tests are a useful tool to guide patient treatment and to test a response before administering medicines. Pharmacogenetic tests can predict potential drug resistance and may be used for determining genotype-based drug dosage. However, their cost-effectiveness as a diagnostic tool is often debatable. In Germany, 47 active ingredients are currently approved. A prior predictive test is required for 39 of these and is recommended for eight...
September 2016: Advances in Therapy
Chiara Fabbri, Concetta Crisafulli, Marco Calabrò, Edoardo Spina, Alessandro Serretti
INTRODUCTION: Depression is responsible for the most part of the personal and socio-economic burden due to psychiatric disorders. Since antidepressant response clusters in families, pharmacogenetics represents a meaningful tool to provide tailored treatments and improve the prognosis of depression. AREAS COVERED: This review aims to summarize and discuss the pharmacogenetics of antidepressant drugs in major depressive disorder, with a focus on the most replicated genes, genome-wide association studies (GWAS), but also on the findings provided by new and promising analysis methods...
October 2016: Expert Opinion on Drug Metabolism & Toxicology
Kelsey Barcomb, Johannes W Hell, Tim A Benke, K Ulrich Bayer
Learning, memory, and cognition are thought to require normal long-term potentiation (LTP) of synaptic strength, which in turn requires binding of the Ca(2+)/calmodulin-dependent protein kinase II (CaMKII) to the NMDA-type glutamate receptor (NMDAR) subunit GluN2B. For LTP induction, many additional required players are known. Here we tested the hypothesis that CaMKII/GluN2B binding also mediates the more elusive maintenance of synaptic strength. Intriguingly, the CaMKII inhibitor tatCN21 reduces synaptic strength only at high concentrations necessary for CaMKII/NMDAR disruption (20 μm) but not at lower concentrations sufficient for kinase inhibition (5 μm)...
July 29, 2016: Journal of Biological Chemistry
Julia Carolin Stingl, Katharina Luise Kaumanns, Katrin Claus, Marie-Louise Lehmann, Kathrin Kastenmüller, Markus Bleckwenn, Gunther Hartmann, Michael Steffens, Dorothee Wirtz, Ann-Kristin Leuchs, Norbert Benda, Florian Meier, Oliver Schöffski, Stefan Holdenrieder, Christoph Coch, Klaus Weckbecker
BACKGROUND: Elderly patients are particularly vulnerable to adverse drug reactions, especially if they are affected by additional risk factors such as multimorbidity, polypharmacy, impaired renal function and intake of drugs with high risk potential. Apart from these clinical parameters, drug safety and efficacy can be influenced by pharmacogenetic factors. Evidence-based recommendations concerning drug-gene-combinations have been issued by international consortia and in drug labels. However, clinical benefit of providing information on individual patient factors in a comprehensive risk assessment aiming to reduce the occurrence and severity of adverse drug reactions is not evident...
2016: BMC Family Practice
Jennifer L Goldman, Susan M Abdel-Rahman
INTRODUCTION: Despite the increased availability of systemic antifungal agents in recent years, the management of invasive fungal disease is still associated with significant morbidity and mortality. Knowledge of a drug's pharmacokinetic behavior is critical for optimizing existing treatment strategies. AREAS COVERED: This review examines the pharmacokinetics of the major drug classes used to treat invasive mycoses including the echinocandins, imidazoles, triazoles, nucleoside analogs, and polyenes...
June 2016: Expert Opinion on Drug Metabolism & Toxicology
Sheng-Dong Pan, Ling-Ling Zhu, Meng Chen, Ping Xia, Quan Zhou
BACKGROUND: Weight-based dosing strategy is still challenging due to poor awareness and adherence. It is necessary to let clinicians know of the latest developments in this respect and the correct circumstances in which weight-based dosing is of clinical relevance. METHODS: A literature search was conducted using PubMed. RESULTS: Clinical indications, physiological factors, and types of medication may determine the applicability of weight-based dosing...
2016: Patient Preference and Adherence
Elizabeth Burke, Rene Love, Pam Jones, Taylor Fife
BACKGROUND: Despite extensive scholastic and professional training, medication management in psychiatry is often relegated to trial-and-error prescribing. Pharmacogenetic testing (PGT) may expedite identification of medications with maximal efficacy and minimal side effects by recognizing individual genetic variability in drug response. OBJECTIVES: This article outlines the background of PGT, explains drug metabolism, and evaluates the impact of PGT. DESIGN: A review of the literature since 2010 found 42 articles regarding PGT in clinical nursing settings on PubMed and ProQuest...
March 23, 2016: Journal of the American Psychiatric Nurses Association
Kathrin Blagec, Katrina M Romagnoli, Richard D Boyce, Matthias Samwald
Background. Pharmacogenomic testing has the potential to improve the safety and efficacy of pharmacotherapy, but clinical application of pharmacogenetic knowledge has remained uncommon. Clinical Decision Support (CDS) systems could help overcome some of the barriers to clinical implementation. The aim of this study was to evaluate the perception and usability of a web- and mobile-enabled CDS system for pharmacogenetics-guided drug therapy-the Medication Safety Code (MSC) system-among potential users (i.e., physicians and pharmacists)...
2016: PeerJ
Aniruddha Agarwal, Sally A Ingham, Keegan A Harkins, Diana V Do, Quan Dong Nguyen
Diabetic retinopathy (DR) and its complications such as diabetic macular edema continue to remain a major cause for legal blindness in the developed world. While the introduction of anti-tVEGF agents has significantly improved visual outcomes of patients with DR, unpredictable response, largely due to genetic polymorphisms, appears to be a challenge with this therapy. With advances in identification of various genetic biomarkers, novel therapeutic strategies consisting of gene transfer are being developed and tested for patients with DR...
February 2016: Pharmacogenomics
Mariacarmela Santarpia, Christian Rolfo, G J Peters, Leticia G Leon, Elisa Giovannetti
Despite many clinical efforts, non-small-cell lung cancer (NSCLC) has a dismal 5-year survival rate of 16%, and high incidence of recurrence. The success of biologically targeted agents, as well as the activity of well-established chemotherapeutic regimens, has been limited by inherited/acquired resistance, and biomarkers to adapt the prescription of anticancer drugs to patients' features are urgently warranted. Areas covered. In oncology, pharmacogenetics should provide the way to select patients who may benefit from a specific therapy that best match the individual and tumor genetic profile, thus allowing maximum activity and minimal toxicity...
2016: Expert Opinion on Drug Metabolism & Toxicology
Emilio G Quetglas, Zlatan Mujagic, Simone Wigge, Daniel Keszthelyi, Sebastian Wachten, Ad Masclee, Walter Reinisch
The search for biomarkers that characterize specific aspects of inflammatory bowel disease (IBD), has received substantial interest in the past years and is moving forward rapidly with the help of modern technologies. Nevertheless, there is a direct demand to identify adequate biomarkers for predicting and evaluating therapeutic response to different therapies. In this subset, pharmacogenetics deserves more attention as part of the endeavor to provide personalized medicine. The ultimate goal in this area is the adjustment of medication for a patient's specific genetic background and thereby to improve drug efficacy and safety rates...
November 28, 2015: World Journal of Gastroenterology: WJG
Susanne B Haga, Jivan Moaddeb, Rachel Mills, Mahesh Patel, William Kraus, Nancy M Allen LaPointe
AIM: To assess feasibility and patient satisfaction with a pharmacist-delivered medication therapy management (MTM) plus pharmacogenetic (PGx) testing service. METHODS: Thirty patients from a cardiology outpatient clinic were enrolled to attend two MTM sessions, undergo PGx testing and complete pre- and post-intervention surveys. Outcome measures included duration of MTM sessions, clinical application of test results, self-reported medication adherence, patient recall of results and perceived value of testing and MTM...
November 2015: Pharmacogenomics
Chenglin Miao, Qichen Cao, Hiroshi T Ito, Homare Yamahachi, Menno P Witter, May-Britt Moser, Edvard I Moser
Hippocampal place cells undergo remapping when the environment is changed. The mechanism of hippocampal remapping remains elusive but spatially modulated cells in the medial entorhinal cortex (MEC) have been identified as a possible contributor. Using pharmacogenetic and optogenetic approaches, we tested the role of MEC cells by examining in mice whether partial inactivation in MEC shifts hippocampal activity to a different subset of place cells with different receptive fields. The pharmacologically selective designer Gi-protein-coupled muscarinic receptor hM4D or the light-responsive microbial proton pump archaerhodopsin (ArchT) was expressed in MEC, and place cells were recorded after application of the inert ligand clozapine-N-oxide (CNO) or light at appropriate wavelengths...
November 4, 2015: Neuron
Simran D S Maggo, Ruth L Savage, Martin A Kennedy
It is well established that variations in genes can alter the pharmacokinetic and pharmacodynamic profile of a drug and immunological responses to it. Early advances in pharmacogenetics were made with traditional genetic techniques such as functional cloning of genes using knowledge gained from purified proteins, and candidate gene analysis. Over the past decade, techniques for analysing the human genome have accelerated greatly as knowledge and technological capabilities have grown. These techniques were initially focussed on understanding genetic factors of disease, but increasingly they are helping to clarify the genetic basis of variable drug responses and adverse drug reactions (ADRs)...
April 2016: Clinical Pharmacokinetics
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