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View article: Enrichment of Germline Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) Pathogenic Variants in Patients With Solid Tumors: Evidence for Increased Cancer Risk
Enrichment of Germline Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) Pathogenic Variants in Patients With Solid Tumors: Evidence for Increased Cancer Risk Open
Introduction Wide‐spread use of cystic fibrosis (CF) transmembrane conductance regulator (CFTR) modulators has resulted in a dramatic increase in life expectancy of people with CF. Historically, CFTR carrier status has been thought to be b…
View article: Evaluation of <i>CYP2C19</i> Clinical Decision Support Alerts to Guide P2Y<sub>12</sub> Inhibitor Prescribing
Evaluation of <i>CYP2C19</i> Clinical Decision Support Alerts to Guide P2Y<sub>12</sub> Inhibitor Prescribing Open
P2Y 12 inhibitor selection involves numerous factors, including CYP2C19 genetics, since evidence demonstrates reduced clopidogrel efficacy in patients with decreased or no function CYP2C19 variants. In 2020, Indiana University health embed…
View article: Return of Clinically Actionable Pharmacogenetic Results From Molecular Tumor Board <scp>DNA</scp> Sequencing Data: Workflow and Estimated Costs
Return of Clinically Actionable Pharmacogenetic Results From Molecular Tumor Board <span>DNA</span> Sequencing Data: Workflow and Estimated Costs Open
Pharmacogenetic testing can prevent severe toxicities from several oncology drug therapies; it also has the potential to improve the outcomes from supportive care drugs. Paired tumor and germline sequencing is increasingly common in oncolo…
View article: Factors Associated With the Recovery of Left Ventricular Ejection Fraction in Patients With Anthracycline-Induced Left Ventricular Dysfunction
Factors Associated With the Recovery of Left Ventricular Ejection Fraction in Patients With Anthracycline-Induced Left Ventricular Dysfunction Open
Background Neurohormonal blocking drugs, like beta-blockers, angiotensin-converting enzyme inhibitors (ACEIs), and angiotensin receptor blockers (ARBs), are recommended for treating anthracycline-induced left ventricular dysfunction (AILVD…
View article: Functional analysis of G6PD variants associated with low G6PD activity in the All of Us Research Program
Functional analysis of G6PD variants associated with low G6PD activity in the All of Us Research Program Open
The glucose-6-phosphate dehydrogenase (G6PD) enzyme protects red blood cells against oxidative damage. Individuals with G6PD-impairing polymorphisms are at risk of hemolytic anemia from oxidative stressors. Prevention of G6PD deficiency-re…
View article: Development of a Multifaceted Program for Pharmacogenetics Adoption at an Academic Medical Center: Practical Considerations and Lessons Learned
Development of a Multifaceted Program for Pharmacogenetics Adoption at an Academic Medical Center: Practical Considerations and Lessons Learned Open
In 2019, Indiana University launched the Precision Health Initiative to enhance the institutional adoption of precision medicine, including pharmacogenetics (PGx) implementation, at university‐affiliated practice sites across Indiana. The …
View article: PCCA variant rs16957301 is a novel AKI risk genotype-specific for patients who receive ICI treatment: Real-world evidence from All of Us cohort
PCCA variant rs16957301 is a novel AKI risk genotype-specific for patients who receive ICI treatment: Real-world evidence from All of Us cohort Open
Background Immune checkpoint inhibitors (ICIs) enhance the immune system’s ability to target and destroy cancer cells by blocking inhibitory pathways. Despite their efficacy, these treatments can trigger immune-related adverse events (irAE…
View article: Functional Analysis of G6PD Variants Associated With Low G6PD Activity in the All of Us Research Program
Functional Analysis of G6PD Variants Associated With Low G6PD Activity in the All of Us Research Program Open
Glucose-6-phosphate dehydrogenase (G6PD) protects red blood cells against oxidative damage through regeneration of NADPH. Individuals with G6PD polymorphisms (variants) that produce an impaired G6PD enzyme are usually asymptomatic, but at …
View article: Analysis of the combined effect of rs699 and rs5051 on angiotensinogen expression and hypertension
Analysis of the combined effect of rs699 and rs5051 on angiotensinogen expression and hypertension Open
Background Hypertension (HTN) involves genetic variability in the renin‐angiotensin system and influences antihypertensive response. We previously reported that angiotensinogen ( AGT ) messenger RNA (mRNA) is endogenously bound by miR‐122‐…
View article: Computational pharmacogenotype extraction from clinical next-generation sequencing
Computational pharmacogenotype extraction from clinical next-generation sequencing Open
Background Next-generation sequencing (NGS), including whole genome sequencing (WGS) and whole exome sequencing (WES), is increasingly being used for clinic care. While NGS data have the potential to be repurposed to support clinical pharm…
View article: Implementation of Clinical Cytochrome P450 3A Genotyping for Tacrolimus Dosing in a Large Kidney Transplant Program
Implementation of Clinical Cytochrome P450 3A Genotyping for Tacrolimus Dosing in a Large Kidney Transplant Program Open
Tacrolimus is a calcineurin inhibitor with a narrow therapeutic range and is metabolized by cytochrome P450 (CYP) isoenzymes CYP3A4 and CYP3A5. The Clinical Pharmacogenetic Implementation Consortium published evidence‐based guidelines for …
View article: Analysis of the Combined Effect of rs699 and rs5051 on Angiotensinogen Expression and Hypertension
Analysis of the Combined Effect of rs699 and rs5051 on Angiotensinogen Expression and Hypertension Open
Hypertension (HTN) involves genetic variability in the renin-angiotensin system and characterizing this variability will help advance precision antihypertensive treatments. We previously reported that angiotensinogen ( AGT ) mRNA is endoge…
View article: Association of QT interval-prolonging drugs with clinical trial eligibility in patients with advanced cancer
Association of QT interval-prolonging drugs with clinical trial eligibility in patients with advanced cancer Open
Introduction Drug-induced prolongation of the heart rate-corrected QT interval (QTc) is associated with increased risk for the potentially fatal arrhythmia torsades de pointes. Due to arrhythmia risk, clinical trials with cancer therapeuti…
View article: Evaluation of US Food and Drug Administration Drug Label Recommendations for Coadministration of Antivirals and Acid‐Reducing Agents
Evaluation of US Food and Drug Administration Drug Label Recommendations for Coadministration of Antivirals and Acid‐Reducing Agents Open
Coadministration with acid‐reducing agents (ARAs), including proton pump inhibitors (PPIs), histamine H 2 ‐receptor antagonists (H 2 blockers), and antacids has been demonstrated to reduce antiviral exposure and efficacy. Therefore, it is …
View article: Clinical Opportunities for Germline Pharmacogenetics and Management of Drug-Drug Interactions in Patients With Advanced Solid Cancers
Clinical Opportunities for Germline Pharmacogenetics and Management of Drug-Drug Interactions in Patients With Advanced Solid Cancers Open
PURPOSE Precision medicine approaches, including germline pharmacogenetics (PGx) and management of drug-drug interactions (DDIs), are likely to benefit patients with advanced cancer who are frequently prescribed multiple concomitant medica…
View article: Life-Threatening Docetaxel Toxicity in a Patient With Reduced-Function CYP3A Variants: A Case Report
Life-Threatening Docetaxel Toxicity in a Patient With Reduced-Function CYP3A Variants: A Case Report Open
Docetaxel therapy occasionally causes severe and life-threatening toxicities. Some docetaxel toxicities are related to exposure, and inter-individual variability in exposure has been described based on genetic variation and drug-drug inter…
View article: CLINICAL OPPORTUNITIES FOR GERMLINE PHARMACOGENETICS AND MANAGEMENT OF DRUG-DRUG INTERACTIONS IN PATIENTS WITH ADVANCED SOLID CANCERS
CLINICAL OPPORTUNITIES FOR GERMLINE PHARMACOGENETICS AND MANAGEMENT OF DRUG-DRUG INTERACTIONS IN PATIENTS WITH ADVANCED SOLID CANCERS Open
PURPOSE Precision medicine approaches, including germline pharmacogenetics (PGx) and management of drug-drug interactions (DDIs), are likely to benefit advanced cancer patients who are frequently prescribed multiple concomitant medications…
View article: Letrozole targets the human ether‐a‐go‐go–related gene potassium current in glioblastoma
Letrozole targets the human ether‐a‐go‐go–related gene potassium current in glioblastoma Open
Aberrant expression of human ether‐a‐go‐go–related gene (hERG) potassium channels has been implicated in the pathophysiology of glioblastoma (GBM). Letrozole has demonstrated efficacy in pre‐clinical GBM models. The objective of this resea…
View article: Neurohormonal Regulation of I <sub>Ks</sub> in Heart Failure: Implications for Ventricular Arrhythmogenesis and Sudden Cardiac Death
Neurohormonal Regulation of I <sub>Ks</sub> in Heart Failure: Implications for Ventricular Arrhythmogenesis and Sudden Cardiac Death Open
Heart failure (HF) results in sustained alterations in neurohormonal signaling, including enhanced signaling through the sympathetic nervous system and renin‐angiotensin‐aldosterone system pathways. While enhanced sympathetic nervous syste…
View article: Progesterone Metabolites Inhibit the Human Ether‐a‐go‐go‐Related Gene and Predict QT Interval Length
Progesterone Metabolites Inhibit the Human Ether‐a‐go‐go‐Related Gene and Predict QT Interval Length Open
A decrease in the human ether‐a‐go‐go‐related gene ( hERG /KCNH2)‐related channel has been linked to intrauterine fetal death. The formation of cytochrome P450 (CYP) 3A‐mediated progesterone metabolites, 6‐beta‐hydroxy‐progesterone (6β‐OHP…
View article: Efavirenz Inhibits the Human Ether‐A‐Go‐Go Related Current (hERG) and Induces QT Interval Prolongation in <i>CYP2B6*6*6</i> Allele Carriers
Efavirenz Inhibits the Human Ether‐A‐Go‐Go Related Current (hERG) and Induces QT Interval Prolongation in <i>CYP2B6*6*6</i> Allele Carriers Open
Efavirenz Induced QTc Interval Prolongation Background Efavirenz (EFV) has been associated with torsade de pointes despite marginal QT interval lengthening. Since EFV is metabolized by the cytochrome P450 (CYP) 2B6 enzyme, we hypothesized …