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Cardiovascular pharmacogenetics

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https://www.readbyqxmd.com/read/28431457/precision-medicine-and-pharmacogenetics-what-does-oncology-have-that-addiction-medicine-does-not
#1
Henry R Kranzler, Rachel V Smith, Robert Schnoll, Afaf Moustafa, Emma Greenstreet-Akman
BACKGROUND AND AIMS: Precision, personalized or stratified medicine, which promises to deliver the right treatment to the right patient, is a topic of international interest in both the lay press and the scientific literature. A key aspect of precision medicine is the identification of biomarkers that predict the response to medications (i.e. pharmacogenetics). We examined why, despite the great strides that have been made in biomarker identification in many areas of medicine, only in oncology has there been substantial progress in their clinical implementation...
April 21, 2017: Addiction
https://www.readbyqxmd.com/read/28421156/the-personalization-of-clopidogrel-antiplatelet-therapy-the-role-of-integrative-pharmacogenetics-and-pharmacometabolomics
#2
REVIEW
Arwa M Amin, Lim Sheau Chin, Dzul Azri Mohamed Noor, Muhamad Ali Sk Abdul Kader, Yuen Kah Hay, Baharudin Ibrahim
Dual antiplatelet therapy of aspirin and clopidogrel is pivotal for patients undergoing percutaneous coronary intervention. However, the variable platelets reactivity response to clopidogrel may lead to outcome failure and recurrence of cardiovascular events. Although many genetic and nongenetic factors are known, great portion of clopidogrel variable platelets reactivity remain unexplained which challenges the personalization of clopidogrel therapy. Current methods for clopidogrel personalization include CYP2C19 genotyping, pharmacokinetics, and platelets function testing...
2017: Cardiology Research and Practice
https://www.readbyqxmd.com/read/28351962/pharmacogenetic-associations-of-%C3%AE-1-adrenergic-receptor-polymorphisms-with-cardiovascular-outcomes-in-the-sps3-trial-secondary-prevention-of-small-subcortical-strokes
#3
Oyunbileg Magvanjav, Caitrin W McDonough, Yan Gong, Leslie A McClure, Robert L Talbert, Richard B Horenstein, Alan R Shuldiner, Oscar R Benavente, Braxton D Mitchell, Julie A Johnson
BACKGROUND AND PURPOSE: Functional polymorphisms (Ser49Gly and Arg389Gly) in ADRB1 have been associated with cardiovascular and β-blocker response outcomes. Herein we examined associations of these polymorphisms with major adverse cardiovascular events (MACE), with and without stratification by β-blocker treatment in patients with a history of stroke. METHODS: Nine hundred and twenty-six participants of the SPS3 trial's (Secondary Prevention of Small Subcortical Strokes) genetic substudy with hypertension were included...
May 2017: Stroke; a Journal of Cerebral Circulation
https://www.readbyqxmd.com/read/28332511/risk-of-acute-myocardial-infarction-after-discontinuation-of-antihypertensive-agents-a-case-control-study
#4
F F Alharbi, P C Souverein, M C de Groot, A H Maitland-van der Zee, A de Boer, O H Klungel
We performed a nested case-control study in a cohort of antihypertensive drug users to assess the association between discontinuation of different antihypertensive agents and the risk of acute myocardial infarction (AMI). Cases and controls were drawn from the Utrecht Cardiovascular Pharmacogenetics database. Patients who were hospitalised for their first AMI were considered cases and controls were not hospitalised for AMI. Antihypertensive users were defined as current users if the index date (date of AMI) fell within the prescribed duration or as discontinuers if this date fell outside the prescribed duration...
March 23, 2017: Journal of Human Hypertension
https://www.readbyqxmd.com/read/28255814/frequency-of-single-nucleotide-platelet-receptor-gene%C3%A2-polymorphism-p2y12-i744t-c-in-coronary-artery-disease-patients-among-tamilian-population
#5
R Priyadharsini, G Umamaheswaran, T A R Raja, A S Arun Kumar, K Subraja, S A Dkhar, S Satheesh, C Adithan, D G Shewade
Several factors contribute to the development of coronary artery disease (CAD). Adenosine diphosphate (ADP) activated P2Y12 receptor also plays a key role in platelet activation and aggregation. It has been found that common variation in the P2Y12 gene was associated with increased platelet aggregation resulting in adverse cardiovascular outcomes. Thus, polymorphisms in the ADP receptor P2Y12 may contribute to the development of CAD. This study aims to determine the frequency distribution of platelet receptor polymorphism P2Y12 (i744T>C) in Tamilian population and to predict its possible role in CAD...
April 2017: Journal of Community Genetics
https://www.readbyqxmd.com/read/28237404/pharmacogenetics-in-cardiovascular-diseases-state-of-the-art-and-implementation-recommendations-of-the-french-national-network-of-pharmacogenetics-rnpgx
#6
Fabien Lamoureux, Thomas Duflot
The use of genomic markers to predict drug response and effectiveness has the potential to improve healthcare by increasing drug efficacy and minimizing adverse effects. Polymorphisms associated with inter-individual variability in drug metabolism, transport, or pharmacodynamics of major cardiovascular drugs have been identified. These include single nucleotide polymorphisms (SNP) affecting clinical outcomes in patients receiving antiplatelet agents, oral anticoagulants and statins. Based on clinical evidence supporting genetic testing in the management of cardiovascular diseases using these drug classes, this short review presents clinical guidance regarding current pharmacogenetics implementation in routine medical practice...
January 30, 2017: Thérapie
https://www.readbyqxmd.com/read/28117133/pharmacogenetics-of-ecstasy-cyp1a2-cyp2c19-and-cyp2b6-polymorphisms-moderate-pharmacokinetics-of-mdma-in-healthy-subjects
#7
Patrick Vizeli, Yasmin Schmid, Katharina Prestin, Henriette E Meyer Zu Schwabedissen, Matthias E Liechti
In vitro studies showed that CYP2C19, CYP2B6, and CYP1A2 contribute to the metabolism of 3,4-methylenedioxymethamphetamine (MDMA, ecstasy) to 3,4-methylenedioxyamphetamine (MDA). However, the role of genetic polymorphisms in CYP2C19, CYP2B6, and CYP1A2 in the metabolism of MDMA in humans is unknown. The effects of genetic variants in these CYP enzymes on the pharmacokinetics and pharmacodynamics of MDMA were characterized in 139 healthy subjects (69 male, 70 female) in a pooled analysis of eight double-blind, placebo-controlled studies...
January 20, 2017: European Neuropsychopharmacology: the Journal of the European College of Neuropsychopharmacology
https://www.readbyqxmd.com/read/28117005/pharmacogenomic-challenges-in-cardiovascular-diseases-examples-of-drugs-and-considerations-for-future-integration-in-clinical-practice
#8
Jérôme Chatelin, Maria G Stathopoulou, Alex-Ander Aldasoro Arguinano, Ting Xie, Sophie Visvikis-Siest
Introduction Even if cardiovascular disease (CVD) drugs are supported by high level proofs, the results of CVD treatment present great disparities: there are still patients dying with supposed optimal treatment, patients facing adverse events and CVD remain the primary cause of death in the world. Pharmacogenomics is the basis of personalisation of the treatment able to allow higher medication success rates. In this review, we will present detailed examples of CVD drugs to highlight the complexity of this challenging field and we will discuss novel concepts that should be considered for a fastest integration of pharmacogenomics in clinical practice of CVD...
January 23, 2017: Current Pharmaceutical Biotechnology
https://www.readbyqxmd.com/read/28057368/genomic-translational-research-paving-the-way-to-individualized-cardiac-functional-analyses-and-personalized-cardiology
#9
REVIEW
Ares Pasipoularides
For most of Medicine's past, the best that physicians could do to cope with disease prevention and treatment was based on the expected response of an average patient. Currently, however, a more personalized/precise approach to cardiology and medicine in general is becoming possible, as the cost of sequencing a human genome has declined substantially. As a result, we are witnessing an era of precipitous advances in biomedicine and bourgeoning understanding of the genetic basis of cardiovascular and other diseases, reminiscent of the resurgence of innovations in physico-mathematical sciences and biology-anatomy-cardiology in the Renaissance, a parallel time of radical change and reformation of medical knowledge, education and practice...
March 1, 2017: International Journal of Cardiology
https://www.readbyqxmd.com/read/27977217/identification-and-characterization-of-trimethylamine-n-oxide-uptake-and-efflux-transporters
#10
Wendy A Teft, Bridget L Morse, Brenda F Leake, Aze Wilson, Sara E Mansell, Robert A Hegele, Richard H Ho, Richard B Kim
Trimethylamine-N-oxide (TMAO) is a recently identified predictor of cardiovascular and chronic kidney disease. TMAO is primarily generated through gut-microbiome mediated conversion of dietary choline and carnitine to TMA, which is converted to TMAO by hepatic flavin monooxygenase 3 (FMO3) and subsequently undergoes renal elimination. We investigated the role of uptake and efflux drug transporters in TMAO disposition in vitro and in vivo. After screening a large array of uptake transporters, we show organic cation transporter 2 (OCT2) is the key transporter for TMAO cellular uptake...
January 3, 2017: Molecular Pharmaceutics
https://www.readbyqxmd.com/read/27932982/impact-of-cyp2c19-variants-on-clinical-efficacy-of-clopidogrel-and-1-year-clinical-outcomes-in-coronary-heart-patients-undergoing-percutaneous-coronary-intervention
#11
Hong Sun, Qiang Qu, Zhen-Fan Chen, Sheng-Lan Tan, Hai-Jun Zhou, Jian Qu, Hui Chen
The impact of pharmacogenetic variants of cytochrome P450 2C19 (CYP2C19) on clopidogrel-mediated effects on platelet inhibition, inflammatory response and endothelial function, as well as risk of major adverse cardiovascular events (MACE), in coronary heart patients undergoing percutaneous coronary intervention (PCI) was investigated. To this end, we assessed the residual platelet aggregation rate (RPA), maximal aggregation rate (MAR) and plasma levels of sCD40L, sP-selectin, MMP-9, sVCAM-1 and sE-selectin after 24 h of PCI in 559 patients treated with clopidogrel and followed up for 1 year for evidence of MACE...
2016: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/27864383/use-of-pharmacogenetic-information-in-the-treatment-of-cardiovascular-disease
#12
REVIEW
Kevin Friede, Josephine Li, Deepak Voora
BACKGROUND: In 1964, Robert A. O'Reilly's research group identified members of a family who required remarkably high warfarin doses (up to 145 mg/day, 20 times the average dose) to achieve appropriate anticoagulation. Since this time, pharmacogenetics has become a mainstay of cardiovascular science, and genetic variants have been implicated in several fundamental classes of medications used in cardiovascular medicine. CONTENT: In this review, we discuss genetic variants that affect drug response to 3 classes of cardiovascular drugs: statins, platelet P2Y12 inhibitors, and anticoagulants...
January 2017: Clinical Chemistry
https://www.readbyqxmd.com/read/27855643/evaluation-of-a-pharmacogenetic-based-warfarin-dosing-algorithm-in-patients-with-low-time-in-therapeutic-range-study-protocol-for-a-randomized-controlled-trial
#13
Leiliane Rodrigues Marcatto, Luciana Sacilotto, Carolina Tosin Bueno, Mirella Facin, Celia Maria Cassaro Strunz, Francisco Carlos Costa Darrieux, Maurício Ibrahim Scanavacca, Jose Eduardo Krieger, Alexandre Costa Pereira, Paulo Caleb Junior Lima Santos
BACKGROUND: Time in therapeutic range (TTR) is a measurement of quality of warfarin therapy and lower TTR values (<50%) are associated with greater risk of thromboembolic and bleeding events. Recently, we developed a pharmacogenetic-based warfarin dosing algorithm specifically calibrated for a Brazilian patient sample. The aims of this study are: to evaluate the impact of a genetic-based algorithm, compared to traditional anticoagulation, in the time to achieve the therapeutic target and in TTR percentage; and to assess the cost-effectiveness of genotype-guided warfarin dosing in a specific cohort of patients with low TTR (<50%) from a tertiary cardiovascular hospital...
November 17, 2016: BMC Cardiovascular Disorders
https://www.readbyqxmd.com/read/27771748/pharmacogenetics-of-stimulant-abuse-liability-association-of-cdh13-variant-with-amphetamine-response-in-a-racially-heterogeneous-sample-of-healthy-young-adults
#14
Adam M Leventhal, Matthew G Kirkpatrick, Mollie S Pester, John E McGeary, Robert M Swift, Steve Sussman, Christopher W Kahler
RATIONALE: A previous genome-wide association study (GWAS) in a predominately Caucasian sample of healthy young adults linked greater amphetamine-induced rewarding effects with the rs3784943 G allele of the cadherin 13 (CDH13; i.e., a cell adhesion molecule implicated in neuronal connectivity) gene. This association has not been subsequently examined, nor has it been studied in Asian populations, which may have greater frequencies of the risk allele. OBJECTIVE: The objective of this study was to examine the association of rs3784943 with amphetamine response in a racially heterogeneous sample (37 % Asian) of healthy young adults...
January 2017: Psychopharmacology
https://www.readbyqxmd.com/read/27757045/pharmacogenomics-of-statins-understanding-susceptibility-to-adverse-effects
#15
REVIEW
Joseph P Kitzmiller, Eduard B Mikulik, Anees M Dauki, Chandrama Murkherjee, Jasmine A Luzum
Statins are a cornerstone of the pharmacologic treatment and prevention of atherosclerotic cardiovascular disease. Atherosclerotic disease is a predominant cause of mortality and morbidity worldwide. Statins are among the most commonly prescribed classes of medications, and their prescribing indications and target patient populations have been significantly expanded in the official guidelines recently published by the American and European expert panels. Adverse effects of statin pharmacotherapy, however, result in significant cost and morbidity and can lead to nonadherence and discontinuation of therapy...
2016: Pharmacogenomics and Personalized Medicine
https://www.readbyqxmd.com/read/27753953/os-08-03-pharmacogenetic-markers-of-survival
#16
Vera Erdman, Ilsia Tuktarova, Timur Nasibullin, Ianina Timasheva, Olga Mustafina
OBJECTIVE: Physiological and biochemical changes during aging alter drug metabolism. Drug intake is increased with age because of cumulative morbidity, in particular, high prevalence of cardiovascular diseases. Antihypertensive medications are the most commonly used drugs. Individual drug sensitivity or resistance may be influenced by the variance of the "pharmacological response" genes.Our purpose was to search for the polymorphic variants of "pharmacological response" genes associated with survival in different age periods...
September 2016: Journal of Hypertension
https://www.readbyqxmd.com/read/27714756/cardiovascular-pharmacogenetics-a-promise-for-genomically-guided-therapy-and-personalized-medicine
#17
REVIEW
M Zaiou, H El Amri
Cardiovascular disease (CVD) is the leading cause of death worldwide. The basic causes of CVD are not fully understood yet. Substantial evidence suggests that genetic predisposition plays a vital role in the physiopathology of this complex disease. Hence, identification of genetic contributors to CVD will likely add diagnostic accuracy and better prediction of an individual's risk. With high-throughput genetics and genomics technology and newer genome-wide study approaches, a number of genetic variations across the human genome were uncovered...
March 2017: Clinical Genetics
https://www.readbyqxmd.com/read/27713329/the-pharmacogenomics-of-anti-hypertensive-therapy
#18
REVIEW
Sandosh Padmanabhan, Laura Paul, Anna F Dominczak
Hypertension is a major public health problem, but measures to reduce blood pressure and thus cardiovascular risk are complicated by the high prevalence of treatment resistance, despite the availability of multiple drugs. Drug side-effects contribute considerably to suboptimal blood pressure control. Clinicians must often rely on empirical methods to match patients with effective drug treatment. Hypertension pharmacogenomics seeks to find genetic predictors of response to drugs that lower blood pressure and to translate this knowledge into clinical practice...
June 1, 2010: Pharmaceuticals
https://www.readbyqxmd.com/read/27672144/enhancing-literacy-in-cardiovascular-genetics-a-scientific-statement-from-the-american-heart-association
#19
Seema Mital, Kiran Musunuru, Vidu Garg, Mark W Russell, David E Lanfear, Rajat M Gupta, Kathleen T Hickey, Michael J Ackerman, Marco V Perez, Dan M Roden, Daniel Woo, Caroline S Fox, Stephanie Ware
Advances in genomics are enhancing our understanding of the genetic basis of cardiovascular diseases, both congenital and acquired, and stroke. These advances include finding genes that cause or increase the risk for childhood and adult-onset diseases, finding genes that influence how patients respond to medications, and the development of genetics-guided therapies for diseases. However, the ability of cardiovascular and stroke clinicians to fully understand and apply this knowledge to the care of their patients has lagged...
October 2016: Circulation. Cardiovascular Genetics
https://www.readbyqxmd.com/read/27662521/patterns-of-antiplatelet-drug-use-after-a-first-myocardial-infarction-during-a-10-year-period
#20
Alfi Yasmina, Anthonius de Boer, Vera H M Deneer, Patrick C Souverein, Olaf H Klungel
AIMS: The aims of the present study were to assess antiplatelet drug use patterns after a first myocardial infarction (MI) and to evaluate the determinants of antiplatelet nonpersistence. METHODS: The present study was conducted in 4690 patients from the Utrecht Cardiovascular Pharmacogenetics cohort with a first MI between 1986 and 2010, who were followed for a maximum of 10 years. Medication use and event diagnosis were obtained from the Dutch PHARMO Record Linkage System...
March 2017: British Journal of Clinical Pharmacology
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