Yan Gong

• PhD, MS
• University of Florida

Dual antiplatelet therapy (DAPT) with aspirin and a P2Y12 receptor inhibitor (clopidogrel, prasugrel, or ticagrelor) is indicated after percutaneous coronary intervention (PCI) to reduce the risk of atherothrombotic events. Approximately 30% of the US population has a CYP2C19 no‐function allele that reduces the effectiveness of clopidogrel, but not...

The nucleos(t)ide analogs require phosphorylation to the pharmacologically active anabolites in cells. We investigated the hypothesis that single-nucleotide polymorphisms (SNPs) in genes that encode transporters and phosphodiesterase (PDE) enzymes involved in tenofovir (TFV), disoproxil fumarate (TDF), and lamivudine (3TC) disposition will be assoc...

The University of Florida Health conducted a pragmatic implementation of a pharmacogenetics (PGx) panel‐based test to guide medications used for supportive care prescribed to patients undergoing chemotherapy. The implementation was in the context of a pragmatic clinical trial for patients with non‐hematologic cancers being treated with chemotherapy...

The ABCD‐GENE score was developed to predict poor response to clopidogrel and includes A ge, B ody mass index, C hronic kidney disease (CKD; estimated glomerular filtration rate [eGFR] < 60 mL/min/1.73 m ² ), D iabetes, and CYP2C19 GENE variants; a score ≥ 10 is predictive of reduced clopidogrel effectiveness after percutaneous coronary interventio...

This study investigates the association between circulating microRNA (miRNA) expression and cardiovascular adverse events (CVAE) in multiple myeloma (MM) patients treated with a carfilzomib (CFZ)-based regimen. A cohort of 60 MM patients from the Prospective Observation of Cardiac Safety with Proteasome Inhibitor (PROTECT) study was analyzed. Among...

Background Cytochrome P450 2C19 (CYP2C19) intermediate and poor metabolizer patients exhibit diminished clopidogrel clinical effectiveness after percutaneous coronary intervention (PCI). However, outcome studies to date have lacked racial diversity. Thus, the impact of CYP2C19 genotype on cardiovascular outcomes in patients treated with clopidogrel...

Hydrocodone, tramadol, codeine, and oxycodone are commonly prescribed opioids that rely on activation by cytochrome P450 2D6 (CYP2D6). CYP2D6 inhibitors can significantly decrease CYP2D6 activity, leading to reduced generation of active metabolites, and impairing pain control. To understand this impact, we assessed emergency department (ED) visits...

As a treatment for relapsed or refractory multiple myeloma (MM), carfilzomib has been associated with a significant risk of cardiovascular adverse events (CVAE). The goals of our study were to evaluate the metabolomic profile of MM patients to identify those at high risk prior to carfilzomib treatment and to explore the mechanisms of carfilzomib‐CV...

Hypertensive patients with a higher proportion of genetic West African ancestry (%GWAA) have better blood pressure (BP) response to thiazide diuretics (TDs) and worse response to β‐blockers (BBs) than those with lower %GWAA, associated with their lower plasma renin activity (PRA). TDs and BBs are suggested to reduce BP in the long term through vaso...

Introduction: The effect of diabetes mellitus (DM) and DM therapy on cardiovascular events (CVE) in patients with prostate cancer (PC) undergoing androgen deprivation therapy (ADT) is unclear in the contemporary era. Methods: Using the Surveillance, Epidemiology, and End Results (SEER)-Medicare linked database, we identified males ≥ 66-year-old wit...

Introduction The CYP2D6 enzyme metabolizes opioids commonly prescribed for cancer‐related pain, and CYP2D6 polymorphisms may contribute to variability in opioid response. We evaluated the feasibility of implementing CYP2D6 ‐guided opioid prescribing for patients with cancer and report pilot outcome data. Methods Adult patients from two cancer cent...

Background Proteasome inhibitor Carfilzomib (CFZ) is effective in treating patients with refractory or relapsed multiple myeloma (MM) but has been associated with cardiovascular adverse events (CVAE) such as hypertension, cardiomyopathy, and heart failure. This study aimed to investigate the contribution of germline genetic variants in protein-codi...

Background Cyclin‐dependent kinase (CDK) 4 and 6 inhibitors have significantly improved survival in patients with hormone receptor–positive metastatic breast cancer. There are few data regarding the epidemiology of cardiovascular adverse events (CVAEs) with these therapies. Methods and Results Using the OneFlorida Data Trust, adult patients withou...

Background Anthracyclines remain a key treatment for many malignancies but can increase the risk of heart failure or cardiomyopathy. Specific guidelines recommend echocardiography and serum cardiac biomarkers such as BNP (B‐type natriuretic peptide) or NT‐proBNP (N‐terminal proBNP) evaluation before and 6 to 12 months after treatment. Our objective...

Abstract Black patients suffer worse outcomes after percutaneous coronary intervention (PCI) than White patients. Inequities in antiplatelet prescribing may contribute to this health disparity. We compared P2Y12 inhibitor prescribing by race following CYP2C19 genotyping to guide antiplatelet therapy selection after PCI. Patients from nine sites tha...

Medication‐related osteonecrosis of the jaw (MRONJ) is a rare but severely debilitating drug‐induced bone disorder in the jawbone region. The first MRONJ was reported in 2003 after bisphosphonates (BPs) exposure. Recently, other drugs such as receptor activator of nuclear factor kappa‐Β ligand (RANKL) inhibitor denosumab and antiangiogenic agents w...

Patients with higher genetic West African ancestry (GWAA) have hypertension (HTN) that is more difficult to treat and have higher rates of cardiovascular diseases (CVD) and differential responses to antihypertensive drugs than those with lower GWAA. The mechanisms underlying these disparities are poorly understood. Using data from 84 ancestry-infor...

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 formation of highly potent metabolites. Individuals with reduced or absent CYP2D6 activity (i.e., int...

Hypertension is a leading risk factor for cardiovascular disease mortality. African Americans (AAs) have the highest prevalence of hypertension in the United States, and to alleviate the burden of hypertension in this population, better control of blood pressure (BP) is needed. Previous studies have shown considerable interpersonal differences in B...

Background: The knowledge of factors influencing disease progression in patients with established coronary heart disease (CHD) is still relatively limited. One potential pathway is related to peroxisome proliferator–activated receptor gamma coactivator-1 alpha (PPARGC1A), a transcription factor linked to energy metabolism which may play a role in t...

This cohort study examines the association between biological aging and all-cause and cardiovascular disease–specific death rates among individuals with cancer.

There are limited comparison data throughout the dosing interval for generic versus brand metoprolol extended‐release (ER) tablets. We compared the pharmacokinetics (PK) and pharmacodynamics (PD) of brand name versus two generic formulations (Drugs 1 and 2) of metoprolol ER tablets with different time to maximum concentration (Tmax) in adults with...

The ABCD‐GENE score was developed to identify patients at risk for diminished antiplatelet effects with clopidogrel after percutaneous coronary intervention (PCI) and utilizes Age, Body mass index, Chronic kidney disease, Diabetes and CYP2C19 GENEtic variants. The objective of this study was to validate the ability of ABCD‐GENE score to predict ris...

We aim to determine the cumulative and comparative risk of cardiovascular events associated with different Immunomodulatory Drugs (iMiDs) and Proteasome Inhibitor (PIs) in Multiple Myeloma (MM) patients through pairwise and network meta-analysis. Electronic searches were conducted using Ovid MEDLINE, EMBASE, CINAHL, Web of Science, and Clinical Tri...

Introduction: Combination therapy of Immunomodulatory drugs (iMiDs) (Thalidomide, Lenalidomide, Pomalidomide) and Proteasome Inhibitors (PIs) (Bortezomib, Carfilzomib, Ixazomib) constitutes the backbone of treatment in MM patients. Cardiotoxic side-effect profile of iMiDs is not well-documented. Although Carfilzomib has been associated with cardiot...

Cardiometabolic disease (CMD) is the most common preventable cause of death in the world. A number of components are included in the spectrum of CMD, such as metabolic syndrome/obesity, hyperglycemia/diabetes, dyslipidemia, and hypertension, which are independently associated with cardiovascular disease risk. These conditions often occur together,...

Plasma renin activity (PRA) is a predictive biomarker of blood pressure (BP) response to antihypertensives in European–American hypertensive patients. We aimed to identify the metabolic signatures of baseline PRA and the linkages with BP response to β-blockers and thiazides. Using data from the Pharmacogenomic Evaluation of Antihypertensive Respons...

Medication‐related osteonecrosis of the jaw (MRONJ) is a rare but serious drug‐related adverse event. To identify pharmacogenomic markers of MRONJ associated with bisphosphonate therapy, we conducted a genome‐wide association study (GWAS) meta‐analysis followed by functional analysis of 5,008 individuals of European ancestry treated with bisphospho...

We sought to identify genome‐wide variants influencing antihypertensive drug response and adverse cardiovascular outcomes, utilizing data from four randomized controlled trials in the International Consortium for Antihypertensive Pharmacogenomics Studies (ICAPS). Genome‐wide antihypertensive drug‐SNP interaction tests for four drug classes (β‐block...

Multiple myeloma (MM) is the second most frequent hematologic cancer in the United States. Carfilzomib (CFZ), an irreversible proteasome inhibitor being used to treat relapsed and refractory MM, has been associated with cardiotoxicity, including heart failure. We hypothesized that a multi-omics approach integrating data from different omics would p...

Importance Accumulating evidence indicates that higher blood pressure (BP) variability from one physician office visit to the next (hereafter referred to as visit-to-visit BP variability) is associated with poor outcomes. Short-term measurement (throughout 1 year) of visit-to-visit BP variability in high-risk older patients may help identify patien...

Nevirapine (NVP) is a non-nucleoside reverse transcriptase inhibitor that is used in the treatment of human immunodeficiency virus (HIV) infection in children younger than 3 years old. Identifying genetic predictors of NVP pharmacokinetics (PK) in young children is important because inter-individual variability in NVP concentrations contributes to...

Aims Inflammation plays an important role in cardiovascular disease (CVD) development. The NOD-like receptor protein-3 (NLRP3) inflammasome contributes to the development of atherosclerosis in animal models. Components of the NLRP3 inflammasome pathway such as interleukin-1β can therapeutically be targeted. Associations of genetically determined in...

Background Immune checkpoint inhibitors (ICIs) are a novel class of anticancer agents that have demonstrated clinical response for both solid and hematological malignancies. ICIs are associated with development of immune-related adverse events including cardiotoxicity. We estimated the incidence of newly diagnosed cardiovascular disease in patients...

Introduction Although the majority of pharmacy schools are teaching pharmacogenetics in their curricula, there is limited coverage of important clinical concepts and pharmacists report low comfortability in utilizing pharmacogenetic results. Objectives To compare the effectiveness of a combined didactic and patient case‐based, interactive teaching...

Cytochrome P450 2D6 (CYP2D6) genotype–guided opioid prescribing is limited. The purpose of this type 2 hybrid implementation-effectiveness trial was to evaluate the feasibility of clinically implementing CYP2D6-guided postsurgical pain management and determine that such an approach did not worsen pain control. Adults undergoing total joint arthropl...

VKORC1 and CYP2C9 genotypes explain less variability in warfarin dose requirements in African Americans (AAs) compared to Europeans. Variants in BCKDK and GATA-4 gene regions, purported to regulate VKORC1 and CYP2C9 expression, have been shown to play an important role in warfarin dose requirements in Europeans and Asians, respectively. We sought t...

Only half of hypertensive patients respond to any given antihypertensive. Heterogeneity in pathophysiologic pathways underlying hypertension (HTN) is a major contributor. Personalizing antihypertensive therapy could improve blood pressure (BP) reduction. The objective of this study was to assess the effect of pragmatic implementation of a personali...

Introduction: Congestive heart failure (CHF) increases hospitalization burden and risk of mortality.; However, currently there are no guidelines for preemptive screening for CHF. This study aimed to identify imaging features to classify past CHF in order to predict future CHF in cardiac magnetic resonance images (CMRIs). Hypothesis: Machine learnin...

Introduction: Cyclin Dependent Kinase (CDK) 4/6 inhibitors are a novel class of cancer therapeutics which have significantly improved survival in patients with hormone receptor positive, HER2 negative metastatic breast cancer. There is little data regarding the epidemiology of cardiotoxicity with these therapies. Methods: Using the OneFlorida Data...

Introduction: Multiple Myeloma (MM) is the second most frequent hematologic cancer in the United States. Carfilzomib (CFZ), a proteasome inhibitor used to treat relapsed and refractory MM, has been associated with cardiotoxicity including heart failure (HF). Hypothesis: We hypothesized that a multi-omics approach integrating data from different omi...

Introduction: Anthracyclines remain a key treatment for many malignancies but can increase the risk of heart failure or cardiomyopathy. Different guidelines recommend echocardiography (echo) and BNP or NT-proBNP evaluation before and 6-12 months after treatment. It is unknown however if racial/ethnic disparities exist in the cardiac surveillance of...

Recent CYP2D6 phenotype standardization efforts by CYP2D6 activity score (AS) are based on limited pharmacokinetic (PK) and pharmacodynamic (PD) data. Using data from two independent clinical trials of metoprolol, we compared metoprolol PK and PD across CYP2D6 AS with the goal of determining whether the PK and PD data support the new phenotype clas...

Current guidelines recommend dual antiplatelet therapy (DAPT) consisting of aspirin and a P2Y12 inhibitors following percutaneous coronary intervention (PCI). CYP2C19 genotype can guide DAPT selection, prescribing ticagrelor or prasugrel for loss-of-function (LOF) allele carriers (genotype-guided escalation). Cost-effectiveness analyses (CEA) are t...

Medication-related osteonecrosis of the jaw (MRONJ) is a rare but serious adverse drug reaction. Our previous whole-exome sequencing study found SIRT1 intronic region SNP rs7896005 to be associated with MRONJ in cancer patients treated with intravenous (IV) bisphosphonates (BPs). This study aimed to identify causal variants for this association. In...

Recent clinical guidelines recommend lower blood pressure (BP) goals for most patients, and recent trends have favored use of automated unattended BP measurements in the office setting to minimize observer error and white-coat effects. Patients attending a routinely scheduled CVD clinic visit were prospectively randomized to BP measured using an at...

Genotyping for CYP2C19 no function alleles to guide antiplatelet therapy after percutaneous coronary intervention (PCI) improves clinical outcomes. Although results for the increased function CYP2C19*17 allele are also reported, its clinical relevance in this setting remains unclear. A collaboration across nine sites examined antiplatelet therapy p...

Background Hypertension and coronary artery disease (CAD) are a prevalent combination in older women, however limited data are available to guide blood pressure (BP) management. We hypothesized that older women with hypertension and CAD may not derive long-term benefit by achieving systolic BP (SBP) < 130 mmHg. Methods We analyzed long-term all-ca...

Advances in cancer treatment have significantly improved the survival of cancer patients, but unfortunately, many of these treatments also have long‐term complications. Cancer treatmement related cardiotoxicities is becoming a significant clinical problem that a new discipline, Cardio‐Oncology, was established to advance the cardiovascular care of...

Background: Carfilzomib (CFZ), a proteasome inhibitor used to treat multiple myeloma (MM), has been associated with risk for cardiotoxicity including heart failure (HF). There is a lack of data on the mechanism underlying CFZ-induced cardiotoxicity. Our study aims to better understand molecular mechanisms of CFZ-related cardiotoxicity by determinin...

Background: Immune checkpoint inhibitors (ICIs) are a novel class of anticancer agents that have demonstrated clinical response for both solid and hematological malignancies. ICIs are associated with development of immune-related adverse events including cardiotoxicity. We estimated the incidence of ICI-related cardiotoxicity in patients treated wi...

Background Immune checkpoint inhibitors (ICIs) are a novel class of anticancer agents that have demonstrated clinical response for both solid and hematological malignancies. ICIs are associated with development of immune-related adverse events including cardiotoxicity. We estimated the incidence of ICI-related cardiotoxicity in patients treated wit...

Background Immune checkpoint inhibitors (ICIs) are a novel class of anticancer agents that have demonstrated clinical response for both solid and hematological malignancies. ICIs are associated with development of immune-related adverse events including cardiotoxicity. We estimated the incidence of newly diagnosed cardiovascular disease ICI-related...

Background: Studies examining the role of factor V Leiden among patients at higher risk of atherothrombotic events, such as those with established coronary heart disease (CHD), are lacking. Given that coagulation is involved in the thrombus formation stage on atherosclerotic plaque rupture, we hypothesized that factor V Leiden may be a stronger ri...

Cardiotoxicity related to cancer therapies has become a serious issue, diminishing cancer treatment outcomes and quality of life. Early detection of cancer patients at risk for cardiotoxicity before cardiotoxic treatments and providing preventive measures are potential solutions to improve cancer patients' quality of life. This study focuses on pre...

Background: Specific combinations of two drug classes are recommended in a variety of clinical situations in the management of hypertension. These preferred combinations are based on complimentary blood pressure (BP) lowering mechanisms or benefit for a concomitant disease. Methods: Using electronic health records (EHR) data from 27,579 ambulato...

Aims: Data regarding the optimal systolic blood pressure (SBP) and heart rate (HR) for coronary artery disease (CAD) patients with hypertension and a history of heart failure (HF) are limited. Accordingly, using data from a large clinical trial, we investigated the association between SBP and heart rate and subsequent adverse outcomes in CAD patie...

Chlorthalidone (CTD) is more potent than hydrochlorothiazide (HCTZ) in reducing blood pressure (BP) in hypertensive patients, though both are plagued with BP response variability. However, there is a void in the literature regarding the genetic determinants contributing to the variability observed in BP response to CTD. We performed a discovery gen...

Cardiotoxicity related to cancer therapies has become a serious issue, diminishing cancer treatment outcomes and quality of life. Early detection of cancer patients at risk for cardiotoxicity before cardiotoxic treatments and providing preventive measures are potential solutions to improve cancer patients's quality of life. This study focuses on pr...

Background Hypertension (HTN) and coronary artery disease (CAD) are a prevalent combination in women, however limited data are available to guide blood pressure (BP) management. We hypothesize older women with HTN and CAD may not derive the same prognostic benefit from systolic BP (SBP) lowering <130 mmHg. Purpose To investigate the long-term mort...

Background Hypertension (HTN) disproportionately affects African Americans (AAs), who respond better to thiazide diuretics than other antihypertensives. Variants of the APOL1 gene found in AAs are associated with a higher rate of kidney disease and play a complex role in cardiovascular disease. Methods AA subjects from four HTN trials (n = 961) (G...

Introduction: Nearly one half of the subjects in SPRINT had their blood pressure (BP) measured absent an observer (unattended), whereas most prior trials have used attended measurement. This has created controversy in interpreting the relationship between achieved systolic BP (SBP) and outcomes in SPRINT. Accordingly, we prospectively examined the...

Background: About half of patients with hypertension (HTN) respond to any given antihypertensive drug. Discordance in pathophysiologic pathways underlying HTN and anti-HTN mechanism of action are major contributors. Personalizing anti-HTN therapy could optimize blood pressure (BP) control. The objective of OPTI-BP was to assess the pragmatic implem...

Background There exists a wide interindividual variability in blood pressure (BP) response to β1-blockers. To identify the genetic determinants of this variability, we performed a pharmacogenomic genome-wide meta-analysis of genetic variants influencing β1-blocker BP response.Methods and ResultsGenome-wide association analysis for systolic BP and d...

Background: Hypertension is a major modifiable risk factor for coronary artery disease (CAD), the main cause of death in women. While association between the two is frequent, limited data exist regarding the feasibility of blood pressure (BP) management and outcomes in women across the spectrum of CAD. Accordingly, we analyzed patient characteristi...

Objective: The purpose of this study was to investigate involvement of the P2X7 receptor in the rare condition, localized aggressive periodontitis. Material and methods: Peripheral blood from 220 African Americans (103 with localized aggressive periodontitis and 117 healthy unrelated controls) was stimulated with lipopolysaccharide from E coli a...

Background: Incomplete hepatitis B virus (HBV) suppression during antiretroviral therapy (ART) in human immunodeficiency virus (HIV) and HBV co-infected patients is common, but underlying factors are not fully elucidated. We hypothesize that genetic factors that influence nucleoside analog pharmacokinetics will affect HBV treatment response. Meth...

European Americans (EA) have a better anti‐hypertensive response to beta‐blockers (βB) compared to African Americans albeit with some variability. We undertook genome wide association study (GWAS) to elucidate the underlying genetic determinants in EA contributing to this variability in blood pressure (BP) response. A discovery GWAS of change in BP...

Resistant hypertension (RHTN), defined as uncontrolled blood pressure (BP) ≥ 140/90 using three or more drugs or controlled BP (<140/90) using four or more drugs, is associated with adverse outcomes, including decline in kidney function. We conducted a genome-wide association analysis in 1194 White and Hispanic participants with hypertension and co...

Background PCSK9 (proprotein convertase subtilisin/kexin type 9) inhibitors effectively lower LDL (low‐density lipoprotein) cholesterol and have been shown to reduce cardiovascular outcomes in high‐risk patients. We used real‐world electronic health record data to characterize use of PCSK9 inhibitors, in addition to standard therapies, according to...

β‐Blockers’ heart rate (HR)‐lowering effect is an important determinant of the effectiveness for this class of drugs, yet it is variable among β‐blocker–treated patients. To date, genetic studies have revealed several genetic signals associated with HR response to β‐blockers. However, these genetic signals have not been consistently replicated acro...

Table S1. List of Participating Clinical Data Research Networks and Data Marts Table S2. Definition of the 3 Patient Groups, Ranked Lowest to Highest Risk Table S3. Diagnostic Codes to Identify Comorbid Conditions

Osteonecrosis of the jaw (ONJ) is a rare but serious drug induced adverse event, mainly associated with the use of antiresorptive medications, such as intravenous (IV) bisphosphonates (BPs) in cancer patients. In this review, we evaluated all the pharmacogenomic association studies for ONJ published up to December 2018. To date, two SNPs (CYP2C8 rs...

BACKGROUND: Genetic variation at chromosome 9p21 is a recognized risk factor for coronary heart disease (CHD). However, its effect on disease progression and subsequent events is unclear, raising questions about its value for stratification of residual risk. METHODS: A variant at chromosome 9p21 (rs1333049) was tested for association with subsequen...

Background: Genetic variation at chromosome 9p21 is a recognized risk factor for coronary heart disease (CHD). However, its effect on disease progression and subsequent events is unclear, raising questions about its value for stratification of residual risk. Methods: A variant at chromosome 9p21 (rs1333049) was tested for association with subseq...

Background: The "GENetIcs of sUbSequent Coronary Heart Disease" (GENIUS-CHD) consortium was established to facilitate discovery and validation of genetic variants and biomarkers for risk of subsequent CHD events, in individuals with established CHD. Methods: The consortium currently includes 57 studies from 18 countries, recruiting 185,614 parti...

Table S1. Sensitivity analysis of SN‐5 (participants prescribed omeprazole only).

Table S3. Change in PedsQL scores.

Table S2. Change in Gasp‐Q scores.

Background: Inter-individual variability in blood pressure (BP) response to antihypertensives has been reported. Although plasma renin activity (PRA) is a potential biomarker for personalizing antihypertensive therapy in European-American (EA) and African-American (AA) hypertensives, clinical utility of PRA-guided prescribing is incompletely under...

β-blockers show variable efficacy as antihypertensives. Herein, we evaluated plasma miRNAs as biomarkers for defining antihypertensive response to β-blockers. Expression of 22 β-blocker pharmacodynamics-related miRNAs was assessed in baseline plasma samples from 30 responders and 30 non-responders to metoprolol from the PEAR-2 study (Discovery). Lo...

Purpose: CYP2D6 bioactivates codeine and tramadol, with intermediate and poor metabolizers (IMs and PMs) expected to have impaired analgesia. This pragmatic proof-of-concept trial tested the effects of CYP2D6-guided opioid prescribing on pain control. Methods: Participants with chronic pain (94% on an opioid) from seven clinics were enrolled int...