Journal ArticleJ Thromb Haemost · December 2024
BACKGROUND: Hematopoietic transcription factor RUNX1 is expressed from proximal P2 and distal P1 promoters to yield isoforms RUNX1 B and C, respectively. The roles of these isoforms in RUNX1 autoregulation and downstream gene regulation in megakaryocytes a ...
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Journal ArticleAm J Cardiol · November 15, 2024
The role of lipoprotein (a) (Lp[a]) in the development of obstructive coronary artery disease (CAD) and high-risk plaque (HRP) in primary prevention patients with stable chest pain is unknown. We sought to evaluate the relation of Lp(a), independent of low ...
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Journal ArticleJACC. Basic to translational science · September 2024
The authors investigated the impact of antiplatelet therapy on the megakaryocyte (MK) and platelet transcriptome. RNA-sequencing was performed on MKs treated with aspirin or P2Y12 inhibitor, platelets from healthy volunteers receiving aspirin or ...
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Journal ArticleNat Commun · August 20, 2024
Platelets are key mediators of atherothrombosis, yet, limited tools exist to identify individuals with a hyperreactive platelet phenotype. In this study, we investigate the association of platelet hyperreactivity and cardiovascular events, and introduce a ...
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Journal ArticleAm J Health Syst Pharm · August 12, 2024
PURPOSE: Pharmacogenetic testing can identify patients who may benefit from personalized drug treatment. However, clinical uptake of pharmacogenetic testing has been limited. Clinical practice guidelines recommend biomarker tests that the guideline authors ...
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Journal ArticleClin Pharmacol Ther · August 2024
The Department of Veterans Affairs (VA) utilizes a pharmacogenomic (PGx) program that analyzes specific "pharmacogenes." This study evaluates the effect that pharmacogenes may have on prevalence of polypharmacy. This retrospective cohort study included pat ...
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Journal ArticleClin Transl Sci · August 2024
Chronic pain is a prevalent condition with enormous economic burden. Opioids such as tramadol, codeine, and hydrocodone are commonly used to treat chronic pain; these drugs are activated to more potent opioid receptor agonists by the hepatic CYP2D6 enzyme. ...
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Journal ArticleAm J Prev Cardiol · June 2024
OBJECTIVES: To determine the relationship between lipoprotein particle size/number with hepatic steatosis (HS), given its association with traditional lipoproteins and coronary atherosclerosis. METHODS: Individuals with available CT data and blood samples ...
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Journal ArticleClin Transl Sci · June 2024
Specific selective serotonin reuptake inhibitors (SSRIs) metabolism is strongly influenced by two pharmacogenes, CYP2D6 and CYP2C19. However, the effectiveness of prospectively using pharmacogenetic variants to select or dose SSRIs for depression is uncert ...
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Journal ArticleJ Clin Invest · May 15, 2024
BACKGROUNDPreclinical studies suggest that cholesterol accumulation leads to insulin resistance. We previously reported that alterations in a monocyte cholesterol metabolism transcriptional network (CMTN) - suggestive of cellular cholesterol accumulation - ...
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Journal ArticleArterioscler Thromb Vasc Biol · February 2024
BACKGROUND: Identifying patients with the optimal risk:benefit for ticagrelor is challenging. The aim was to identify ticagrelor-responsive platelet transcripts as biomarkers of platelet function and cardiovascular risk. METHODS: Healthy volunteers (n=58, ...
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Journal ArticlePharmacogenomics · February 2024
Aim: Understanding barriers and facilitators to pharmacogenomics (PGx) implementation and how to structure a clinical program with the Veterans Health Administration (VA). Materials & methods: Healthcare provider (HCP) survey at 20 VA facilities assessing ...
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Journal ArticlePharmacogenomics · 2024
Aim: To survey Veterans Health Administration providers who prescribed tramadol or codeine to patients with known genotyping for cytochrome 2D6 (CYP2D6) to ascertain awareness of their patient's pharmacogenetic (PGx) test status, whether these results infl ...
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Journal ArticleJ Pharm Policy Pract · December 11, 2023
Pharmacogenetic (PGx) testing before initiation of thiopurine treatment and CBC monitoring post-initiation helps avoid adverse events and ensure patient safety. This study aims to evaluate trends in PGx testing and CBC monitoring among Veterans prescribed ...
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Journal ArticlemedRxiv · October 26, 2023
BACKGROUND: CYP2C19 loss-of-function (LOF) alleles decrease the antiplatelet effect of clopidogrel following percutaneous coronary intervention (PCI) in patients presenting with acute coronary syndrome (ACS). The impact of genotype in stable ischemic heart ...
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Journal ArticleJ Pers Med · September 9, 2023
We applied implementation science frameworks to identify barriers and facilitators to veterans' acceptance of pharmacogenomic testing (PGx), which was made available as a part of clinical care at 25 VA medical centers. We conducted 30 min interviews with v ...
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Journal ArticleAm J Health Syst Pharm · August 4, 2023
PURPOSE: To describe the implementation of clinical decision support tools for alerting prescribers of actionable drug-gene interactions in the Veterans Health Administration (VHA). SUMMARY: Drug-gene interactions have been the focus of clinicians for year ...
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Journal ArticleClin Pharmacol Ther · August 2023
Pharmacogenetics can improve clinical outcomes by reducing adverse drug effects and enhancing therapeutic efficacy for commonly used drugs that treat a wide range of cardiovascular diseases. One of the major barriers to the clinical implementation of cardi ...
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Journal ArticleJ Am Heart Assoc · June 6, 2023
Background The interplay between branched-chain amino acid (BCAA) metabolism, an important pathway in adiposity and cardiometabolic disease, and visceral adipose depots such as hepatic steatosis (HS) and epicardial adipose tissue is unknown. We leveraged t ...
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Journal ArticleEur Heart J Qual Care Clin Outcomes · April 26, 2023
AIMS: CYP2C19-guided P2Y12 inhibitor selection can reduce cardiovascular (CV) events and bleeding in patients with acute coronary syndromes (ACSs) post-percutaneous coronary intervention (PCI). The 12-month cost-effectiveness of CYP2C19-guided P2Y12 inhibi ...
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Journal ArticleCardiovasc Res · March 31, 2023
AIMS: Gene expression biosignatures may hold promise to individualize antiplatelet therapy in conjunction with current guidelines and risk scores. The Aspirin Response Signature (ARS) score is comprised of a weighted sum of correlated, pro-thrombotic gene ...
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Journal ArticlePain · December 1, 2022
Response to analgesic therapy is influenced by several factors including genetics and drug-drug interactions. Pharmacogenetic (PGx) variants in the CYP2D6 gene modify response to opioids by altering drug metabolism. We sought to determine the potential imp ...
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Journal ArticleHepatol Commun · December 2022
Cardiovascular disease (CVD) is the leading cause of mortality in adults with hepatic steatosis (HS). However, risk factors for CVD in HS are unknown. We aimed to identify factors associated with coronary artery disease (CAD) and incident major adverse car ...
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Journal ArticlePlatelets · November 17, 2022
Aspirin's clinical efficacy may be influenced by body weight and mass. Although inadequate platelet inhibition by aspirin is suggested as responsible, evidence for this in non-diabetic patients is sparse. We investigated the influence of body weight and ma ...
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Journal ArticleAm Heart J · October 2022
A polygenic risk score (PGS) is associated with obstructive coronary artery disease (CAD) independent of traditional risk factors. Coronary computed tomography angiography (CTA) can characterize coronary plaques, including features of highrisk CAD. However ...
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Journal ArticleClin Transl Sci · October 2022
Opioid prescribing for postoperative pain management is challenging because of inter-patient variability in opioid response and concern about opioid addiction. Tramadol, hydrocodone, and codeine depend on the cytochrome P450 2D6 (CYP2D6) enzyme for formati ...
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Journal ArticleACR Open Rheumatol · August 2022
OBJECTIVE: The study objective was to identify differences in gene expression between treatment responders (TRs) and treatment non-responders (TNRs) diagnosed with juvenile dermatomyositis (JDM). METHODS: Gene expression analyses were performed using whole ...
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Journal ArticleJACC Cardiovasc Imaging · August 2022
BACKGROUND: Increased inflammation and myocardial injury can be observed in the absence of myocardial infarction or obstructive coronary artery disease (CAD). OBJECTIVES: The authors determined whether biomarkers of inflammation and myocardial injury-inter ...
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Journal ArticleJAMA · July 12, 2022
IMPORTANCE: Selecting effective antidepressants for the treatment of major depressive disorder (MDD) is an imprecise practice, with remission rates of about 30% at the initial treatment. OBJECTIVE: To determine whether pharmacogenomic testing affects antid ...
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Journal ArticlePer Med · July 2022
Both transcriptomics and metabolomics hold promise for identifying acute coronary syndrome (ACS) but they have not been used in combination, nor have dynamic changes in levels been assessed as a diagnostic tool. We assessed integrated analysis of periphera ...
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Journal ArticleBr J Clin Pharmacol · May 2022
Aspirin has known effects beyond inhibiting platelet cyclooxygenase-1 (COX-1) that have been incompletely characterized. Transcriptomics can comprehensively characterize the on- and off-target effects of medications. We used a systems pharmacogenomics appr ...
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Journal ArticleClin Pharmacol Ther · May 2022
The SLCO1B1 genotype is known to influence patient adherence to statin therapy, in part by increasing the risk for statin-associated musculoskeletal symptoms (SAMSs). The SLCO1B1*5 allele has previously been associated with simvastatin discontinuation and ...
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Journal ArticleClin Pharmacol Ther · May 2022
Statins reduce cholesterol, prevent cardiovascular disease, and are among the most commonly prescribed medications in the world. Statin-associated musculoskeletal symptoms (SAMS) impact statin adherence and ultimately can impede the long-term effectiveness ...
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Journal ArticleValue Health · April 2022
OBJECTIVES: A cost-effectiveness analysis comparing comprehensive genomic profiling (CGP) of 10 oncogenes, targeted gene panel testing (TGPT) of 4 oncogenes, and no tumor profiling over the lifetime for patients with metastatic lung adenocarcinoma from the ...
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Journal ArticleScientific reports · April 2022
Myocardial injury after non-cardiac surgery (MINS) is common. We investigated the incidence and outcomes of MINS, and mechanistic underpinnings using pre-operative whole blood gene expression profiling in a prospective cohort study of individuals undergoin ...
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Journal ArticlePharmacogenomics · November 2021
Aim: The first Plan-Do-Study-Act cycle for the Veterans Affairs Pharmacogenomic Testing for Veterans pharmacogenomic clinical testing program is described. Materials & methods: Surveys evaluating implementation resources and processes were distributed to i ...
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Journal ArticleWest J Emerg Med · September 23, 2021
INTRODUCTION: Emergency departments (ED) use many medications with a range of therapeutic efficacy and potential significant side effects, and many medications have dosage adjustment recommendations based on the patient's specific genotype. How frequently ...
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Journal ArticleSci Adv · September 10, 2021
Given the evidence for a hyperactive platelet phenotype in COVID-19, we investigated effector cell properties of COVID-19 platelets on endothelial cells (ECs). Integration of EC and platelet RNA sequencing revealed that platelet-released factors in COVID-1 ...
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Journal ArticleClin Gastroenterol Hepatol · July 2021
BACKGROUND & AIMS: Hepatic steatosis has been associated with increased risk of major adverse cardiovascular events (MACE) but it is not clear whether steatosis is independently associated with risk of MACE. We investigated whether steatosis is associated ...
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Journal ArticleGenet Med · July 2021
PURPOSE: A critical gap in the adoption of genomic medicine into medical practice is the need for the rigorous evaluation of the utility of genomic medicine interventions. METHODS: The Implementing Genomics in Practice Pragmatic Trials Network (IGNITE PTN) ...
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Journal ArticleJ Thromb Thrombolysis · February 2021
Platelet gene polymorphisms are associated with variable on-treatment platelet reactivity and vary by race. Whether differences in platelet reactivity and aspirin or ticagrelor exist between African-American and European-Americans remains poorly understood ...
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Journal ArticlePharmacogenomics · February 2021
In 2019, the Veterans Affairs (VA), the largest integrated US healthcare system, started the Pharmacogenomic Testing for Veterans (PHASER) clinical program that provides multi-gene pharmacogenomic (PGx) testing for up to 250,000 veterans at approximately 5 ...
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Journal ArticlePharmacogenomics · January 2021
The North Carolina Precision Health Collaborative is an interdisciplinary, public-private consortium of precision health experts who strategically align statewide resources and strengths to elevate precision health in the state and beyond. Pharmacogenomics ...
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Journal ArticlePharmgenomics Pers Med · 2021
OBJECTIVE: The delivery of pharmacogenetic (PGx) testing has primarily been through clinical and hospital settings. We conducted a study to explore the feasibility of delivering PGx testing through community pharmacies, a less-studied setting. METHODS: We ...
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Journal ArticlePharmgenomics Pers Med · 2021
OBJECTIVE: This study assessed pharmacist experiences with delivering pharmacogenetic (PGx) testing in independent community pharmacies. METHODS: We conducted a cluster randomized trial of independent community pharmacies in North Carolina randomized to pr ...
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ConferenceCirculation · November 17, 2020
Introduction:
CYP2C19 reduced function (RF) alleles (*2, *3) have been shown to impair clopidogrel effectiveness following percutaneous coronary intervention (PCI) in the setting of acute coronary syn ...
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ConferenceCirculation · November 17, 2020
Introduction:
Atorvastatin is commonly prescribed to prevent cardiovascular disease; however, long-term adherence can be eroded by statin associated musculoskeletal symptoms (SAMS). Genetic variants i ...
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Journal ArticleJ Mol Diagn · October 2020
Pharmacogenetics (PGx) testing can be used for detecting genetic variations that may affect an individual's anticipated metabolism of, or response to, medications. Although several studies have focused on developing tools for delivering results from PGx te ...
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Journal ArticleJ Am Heart Assoc · July 21, 2020
Background There are sex differences in the efficacy and safety of aspirin for the prevention of myocardial infarction and stroke. Whether this is explained by underlying differences in platelet reactivity and aspirin response remains poorly understood. Me ...
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Journal ArticlePharmacogenomics · April 2020
Aim: To investigate the current state of TPMT testing at a single-academic medical center. Methods: Single-center, retrospective chart review for patients newly prescribed a thiopurine. Data collection and evaluation included the prevalence and timing of T ...
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Journal ArticleCirc Res · February 14, 2020
RATIONALE: Longitudinal studies are required to distinguish within versus between-individual variation and repeatability of gene expression. They are uniquely positioned to decipher genetic signal from environmental noise, with potential application to gen ...
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Journal ArticleValue Health · January 2020
OBJECTIVE: To evaluate the cost-effectiveness of multigene testing (CYP2C19, SLCO1B1, CYP2C9, VKORC1) compared with single-gene testing (CYP2C19) and standard of care (no genotyping) in acute coronary syndrome (ACS) patients undergoing percutaneous coronar ...
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Journal ArticlePLoS One · 2020
Statins are used to lower cholesterol and prevent cardiovascular disease. Musculoskeletal side effects known as statin associated musculoskeletal symptoms (SAMS), are reported in up to 10% of statin users, necessitating statin therapy interruption and incr ...
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Journal ArticleLupus · December 2019
BACKGROUND: Women with lupus have an increased risk of preeclampsia and preterm birth, and aspirin 81 mg/day is recommended as a preventative measure for preeclampsia. This pilot study quantified the association between a 60-gene aspirin response signature ...
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Journal ArticlePlatelets · 2019
In the PLATelet inhibition and patient Outcomes (PLATO) study, the P2Y12 inhibitors ticagrelor and clopidogrel were compared in the treatment of acute coronary syndromes (ACS). Ticagrelor was shown to reduce occurrence of the primary end point - a composit ...
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Journal ArticlePLoS One · 2019
BACKGROUND: The heart is a metabolically active organ, and plasma acylcarnitines are associated with long-term risk for myocardial infarction. We hypothesized that myocardial ischemia from cardiac stress testing will produce dynamic changes in acylcarnitin ...
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Journal ArticleCirc Genom Precis Med · September 2018
BACKGROUND: Outcomes of tailoring statin-type based on solute carrier organic anion transporterfamily member 1B1 ( SLCO1B1)pharmacogenetic toxicity information on patient, provider, and pharmacological outcomes are unknown. METHODS: The trial randomized 15 ...
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Journal ArticleBMC Med Genomics · January 12, 2018
BACKGROUND: Cardiovascular disease and its sequelae are major causes of global mortality, and better methods are needed to identify patients at risk for future cardiovascular events. Gene expression analysis can inform on the molecular underpinnings of ris ...
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Chapter · January 1, 2018
This chapter will apply the principles and concepts introduced in the "Pharmacogenetics and Pharmacogenomics" chapter in volume 2, namely, discussion of four classes of genetic variants that underlie drug response to cardiovascular agents: (1) pharmacokine ...
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Journal ArticleCirculation · September 5, 2017
BACKGROUND: PCTP (phosphatidylcholine transfer protein) regulates the intermembrane transfer of phosphatidylcholine. Higher platelet PCTP expression is associated with increased platelet responses on activation of protease-activated receptor 4 thrombin rec ...
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Journal ArticleCirc Cardiovasc Genet · August 2017
There have been major advances in our knowledge of the contribution of DNA sequence variations to cardiovascular disease and stroke. However, the inner workings of the body reflect the complex interplay of factors beyond the DNA sequence, including epigene ...
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Journal ArticlePharmacogenomics · March 2017
AIM: To describe the rationale and design of a study evaluating the delivery of pharmacogenetic (PGx) testing in community pharmacies. Study rationale: Pharmacists have expressed interest in offering PGx testing; however, their lack of knowledge and experi ...
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Journal ArticleAm Heart J · February 2017
BACKGROUND: Identifying predictors of coronary artery disease (CAD)-related procedures and events remains a priority. METHODS: We measured an age- and sex-specific gene expression score (ASGES) previously validated to detect obstructive CAD (oCAD) in sympt ...
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Journal ArticleClin Chem · January 2017
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 ...
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Chapter · January 1, 2017
The goal of pharmacogenomics is to provide the right dose of the right drug to the right patient. The vast majority of current drug response biomarkers can be classified into four general categories: pharmacokinetics, pharmacodynamics, disease pathway, and ...
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Journal ArticlePLoS One · 2017
HMG-CoA reductase inhibitors (or "statins") are important and commonly used medications to lower cholesterol and prevent cardiovascular disease. Nearly half of patients stop taking statin medications one year after they are prescribed leading to higher cho ...
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ConferenceBlood · December 2, 2016
AbstractTranscription factor (TF) mutations are increasingly recognized to play a major role in inherited platelet abnormalities. RUNX1, a major hematopoietic TF, acts in a combinatorial manner with other TF ...
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Journal ArticleEBioMedicine · September 2016
Aspirin prevents cardiovascular disease and colon cancer; however aspirin's inhibition of platelet COX-1 only partially explains its diverse effects. We previously identified an aspirin response signature (ARS) in blood consisting of 62 co-expressed transc ...
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Journal ArticleAtherosclerosis · November 2015
BACKGROUND: Carotid artery intima media thickness (IMT) in human is a marker of subclinical atherosclerosis with high heritability. Many genome-wide association studies (GWAS) were performed in European and American populations, yet discovery efforts have ...
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Journal ArticleEur Heart J · August 1, 2015
AIMS: Ticagrelor, a direct-acting P2Y12-receptor antagonist, is rapidly absorbed and partly metabolized to the major metabolite AR-C124910XX (ARC). To identify single-nucleotide polymorphisms (SNPs) associated with pharmacokinetics of ticagrelor and clinic ...
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Journal ArticleJ Cardiovasc Transl Res · August 2015
Over the past 10-15 years, developments in gene expression profiling have opened new arenas for the discovery of important factors in the pathogenesis of numerous disease processes, including coronary artery disease. Messenger RNA and microRNA are differen ...
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Journal ArticlePharmgenomics Pers Med · 2015
In recent years, substantial effort has been made to better understand the influence of genetic factors on the efficacy and safety of numerous medications. These investigations suggest that the use of pharmacogenetic data to inform physician decision-makin ...
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Journal ArticlePLoS One · 2015
Module-based analysis (MBA) aims to evaluate the effect of a group of biological elements sharing common features, such as SNPs in the same gene or metabolites in the same pathways, and has become an attractive alternative to traditional single bio-element ...
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Journal ArticlePharmacogenomics · 2015
AIM: SLCO1B1 variants are associated with intermediate outcomes that may increase risk of death/myocardial infarction (MI) in statin-treated patients. PATIENTS & METHODS: In high-risk Caucasians undergoing cardiac catheterization, we tested the association ...
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Journal ArticlePLoS One · 2015
BACKGROUND: Influenza infection is associated with myocardial infarction (MI), suggesting that respiratory viral infection may induce biologic pathways that contribute to MI. We tested the hypotheses that 1) a validated blood gene expression signature of r ...
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Journal ArticleClin Pharmacol Ther · October 2014
Statins are widely used lipid-lowering drugs that are effective in reducing cardiovascular disease risk. Although they are generally well tolerated, they can cause muscle toxicity, which can lead to severe rhabdomyolysis. Research in this area has been ham ...
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Journal ArticleClin Pharmacol Ther · October 2014
Simvastatin is among the most commonly used prescription medications for cholesterol reduction. A single coding single-nucleotide polymorphism, rs4149056T>C, in SLCO1B1 increases systemic exposure to simvastatin and the risk of muscle toxicity. We summariz ...
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Journal ArticleClinical Pharmacology and Therapeutics · October 1, 2014
Statins are widely used lipid-lowering drugs that are effective in reducing cardiovascular disease risk. Although they are generally well tolerated, they can cause muscle toxicity, which can lead to severe rhabdomyolysis. Research in this area has been ham ...
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Journal ArticleJ Thorac Cardiovasc Surg · April 2014
OBJECTIVE: Recently, the role of β-blockers (BBs) in reducing perioperative mortality has been challenged. The conflicting results might have resulted from the extent of BB metabolism by the cytochrome P-450 (CYP2D6) isoenzyme. The purpose of the present s ...
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Journal ArticleJ Pers Med · March 27, 2014
Statin adherence is often limited by side effects. The SLCO1B1*5 variant is a risk factor for statin side effects and exhibits statin-specific effects: highest with simvastatin/atorvastatin and lowest with pravastatin/rosuvastatin. The effects of SLCO1B1*5 ...
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Journal ArticleJ Am Coll Cardiol · October 1, 2013
OBJECTIVES: The aim of this study was to develop ribonucleic acid (RNA) profiles that could serve as novel biomarkers for the response to aspirin. BACKGROUND: Aspirin reduces death and myocardial infarction (MI), suggesting that aspirin interacts with biol ...
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Journal ArticleSci Transl Med · September 18, 2013
Improved ways to diagnose acute respiratory viral infections could decrease inappropriate antibacterial use and serve as a vital triage mechanism in the event of a potential viral pandemic. Measurement of the host response to infection is an alternative to ...
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Journal ArticlePharmgenomics Pers Med · 2013
Pharmacogenetic testing refers to a type of genetic test to predict a patient's likelihood to experience an adverse event or not respond to a given drug. Despite revision to several labels of commonly prescribed drugs regarding the impact of genetic variat ...
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ConferenceBlood · November 16, 2012
AbstractAbstract 2326Human mature red blood cells (RBC) and platelets are both terminally differentiated cells lacking nuclei. However, these two cell types do possess a dive ...
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Journal ArticleJ Am Coll Cardiol · July 3, 2012
Pharmacogenetics primarily uses genetic variation to identify subgroups of patients who may respond differently to a certain medication. Since its first description, the field of pharmacogenetics has expanded to study a broad range of cardiovascular drugs ...
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Journal ArticleClin Pharmacol Ther · July 2012
Cholesterol reduction from statin therapy has been one of the greatest public health successes in modern medicine. Simvastatin is among the most commonly used prescription medications. A non-synonymous coding single-nucleotide polymorphism (SNP), rs4149056 ...
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Journal ArticleJ Thromb Thrombolysis · April 2012
To develop an integrated metric of non-COX-1-dependent platelet function (NCDPF) to measure the temporal response to aspirin in healthy volunteers and diabetics. NCDPF on aspirin demonstrates wide variability, despite suppression of COX-1. Although a varie ...
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Journal ArticleNat Rev Cardiol · August 9, 2011
Considerable variability exists in how individual patients respond to oral antiplatelet therapy, specifically to aspirin and to P2Y(12)-receptor inhibitors such as clopidogrel. This variability translates to differences in clinical outcomes and might in pa ...
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Journal ArticlePharmacogenomics · August 2011
In 2003 Duke University (Durham, NC, USA) launched the Institute for Genome Sciences & Policy (IGSP) as an interdisciplinary network of centers comprised of scientists, engineers and physicians, as well as experts in law, business, economics public policy ...
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Journal ArticleAm Heart J · July 2011
BACKGROUND: We hypothesized that single-nucleotide polymorphisms (SNPs) associated with heightened in vitro platelet function during aspirin exposure (which we define as "laboratory aspirin resistance") would be associated with greater risk for death, myoc ...
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Journal ArticleJ Cardiovasc Electrophysiol · August 1, 2010
INTRODUCTION: Catheter-directed atrial fibrillation (AF) ablation is contraindicated among patients with left atrial appendage (LAA) thrombus. The prevalence of LAA thrombus among fully anticoagulated patients undergoing AF ablation is unknown. METHODS AND ...
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Journal ArticleClin Pharmacol Ther · April 2010
Warfarin demonstrates a wide interindividual variability in response that is mediated partly by variants in cytochrome P450 2C9 (CYP2C9) and vitamin K 2,3-epoxide reductase complex subunit 1 (VKORC1). It is not known whether variants in calumenin (CALU) (v ...
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Journal ArticleCurrent Cardiovascular Risk Reports · December 1, 2009
Statins (inhibitors of the enzyme 3-hydroxy-3-methylglutaryl-coenzyme A reductase) are widely prescribed medications for the prevention of incident and recurrent cardiovascular disease events and death. They are powerful assets in the current arsenal of ca ...
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Journal ArticleAMIA Annu Symp Proc · November 14, 2009
Prior to clinical use, pharmacogenetic tests should be systematically evaluated for their clinical validity and utility. Here, we evaluated whether the publicly available, online Pharmacogenomics Knowledge Base (PharmGKB) could facilitate such assessments ...
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Journal ArticleJ Am Coll Cardiol · October 20, 2009
OBJECTIVES: We sought to identify single nucleotide polymorphisms associated with mild statin-induced side effects. BACKGROUND: Statin-induced side effects can interfere with therapy. Single nucleotide polymorphisms in cytochrome P450 enzymes impair statin ...
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Journal ArticleCirc Cardiovasc Genet · December 2008
BACKGROUND: There is interindividual variation in low-density lipoprotein cholesterol (LDLc) lowering by statins and limited study into the genetic associations of the dose dependant LDLc lowering by statins. METHODS AND RESULTS: Five hundred nine patients ...
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Journal ArticleClin Pharmacol Ther · September 2008
Initiation of warfarin therapy using trial-and-error dosing is problematic. Our goal was to develop and validate a pharmacogenetic algorithm. In the derivation cohort of 1,015 participants, the independent predictors of therapeutic dose were: VKORC1 polymo ...
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Journal ArticleBlood · September 1, 2007
High variability in drug response and a narrow therapeutic index complicate warfarin therapy initiation. No existing algorithm provides recommendations on refining the initial warfarin dose based on genetic variables, clinical data, and international norma ...
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Journal ArticlePharmacogenomics · July 2005
Vitamin K antagonists (coumarins) are widely-used oral anticoagulants for the prevention of venous thromboembolism and strokes. Wide inter-individual variation in dose response and frequent bleeds characterize the initiation of coumarin therapy. Over the p ...
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Journal ArticleThromb Haemost · April 2005
Cytochrome P-450 2C9 (CYP2C9) polymorphisms (CYP2C9*2 and CYP2C9*3) reduce the clearance of warfarin, increase the risk of bleeding, and prolong the time to stable dosing. Whether prospective use of a retrospectively developed algorithm that incorporates C ...
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Journal ArticleDrugs Today (Barc) · March 2004
The Human Genome Project heralds new opportunities for pharmacogenetics, the use of genetics to individualize the application of pharmaceuticals in the practice of medicine (1-3). Single nucleotide polymorphisms (SNPs) and other genetic variants in genes r ...
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Journal ArticleJ Thromb Thrombolysis · April 2003
Mesenteric vein thrombosis (MVT) is a distinct clinical cause of intestinal ischemia representing 5-15% of all ischemic events. MVT has acute, subacute, and chronic presentations and an underlying cause can be found in nearly 75% of cases. Exogenous hormon ...
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Journal ArticleMetabolism · June 1999
The effect of prolonged exposure to a reduced fraction of inspired oxygen ([FiO2] 0.17 for 3 days) on maternal glucose kinetics, placental glucose transporters GLUT1 and GLUT3, and fetal growth was examined in rat pregnancy. Arterial and venous catheters w ...
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Journal ArticleProc Natl Acad Sci U S A · December 22, 1998
Kss1, a yeast mitogen-activated protein kinase (MAPK), in its unphosphorylated (unactivated) state binds directly to and represses Ste12, a transcription factor necessary for expression of genes whose promoters contain filamentous response elements (FREs) ...
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Journal ArticleGenes Dev · September 15, 1998
The mitogen-activated protein kinase (MAPK) Kss1 has a dual role in regulating filamentous (invasive) growth of the yeast Saccharomyces cerevisiae. The stimulatory function of Kss1 requires both its catalytic activity and its activation by the MAPK/ERK kin ...
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