Author ORCID Identifier
https://orcid.org/0000-0003-4406-1473
Defense Date
2024
Document Type
Dissertation
Degree Name
Doctor of Philosophy
Department
Pharmaceutical Sciences
First Advisor
Elvin Price
Second Advisor
Joseph McClay
Third Advisor
Dave Dixon
Fourth Advisor
Ana Diallo
Fifth Advisor
Elizabeth Prom-Wormley
Abstract
Background: Heart disease remains a leading cause of death in the country, with significant ethnic disparities. Filipino Americans (FAs), the third-largest Asian subgroup in U.S., face an elevated burden of dyslipidemia, a primary modifiable risk factor for heart disease. Objectives: This community-based study addresses critical knowledge gaps by characterizing the cardiometabolic and genetic factors contributing to dyslipidemia among FAs and implications for personalized cardiovascular drug therapies, particularly statin pharmacogenomics (PGx). Methods: We characterized dyslipidemia prevalence in FAs and major ethnic subgroups using nationally representative NHANES data. We examined associations between uric acid (UA) levels and lipid profiles, adjusting for genetic and non-genetic factors. We also characterized the allele frequencies of genetic variants with PGx relevance using a predesigned PGx (120-SNP) TaqMan® OpenArray® panel. Results: FAs had the highest rates of elevated triglycerides, particularly in middle-aged adults. FA men showed worse lipid profiles than FA women and men from other ethnic groups, though FAs generally demonstrated higher HDL-C levels. While elevated UA showed initial associations with adverse lipid profiles, these relationships largely diminished after adjustment, except for a threshold effect on TG at moderate UA levels. We identified significant associations between the APOE-e2 variant and lipid variations. Traditional risk factors including age, BMI, metabolic syndrome, and statin use emerged as strong predictors of lipid parameters. FA participants had the highest frequencies of decreased function ABCG2 among Europeans and African Americans, while the no function SLCO1B1*15 was common. Conversely, FAs had more normal function CYP2C9 variants with rare no function alleles. Conclusions: This dissertation provides insights into cardiovascular health challenges in FAs and supports incorporating PGx data into clinical decision-making to optimize statin therapy. This work contributes to the broader mission of reducing health disparities by promoting PGx research in underrepresented populations and advancing personalized medicine approaches that account for ethnic diversity.
Rights
© The Author
Is Part Of
VCU University Archives
Is Part Of
VCU Theses and Dissertations
Date of Submission
12-12-2024
Included in
Cardiovascular Diseases Commons, Epidemiology Commons, Other Pharmacy and Pharmaceutical Sciences Commons