Cardiometabolic Genomics and Pharmacogenomics in Filipino Americans: A Cross-Sectional Study

Abstract

Heart disease (HD) 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 HD. 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). The first aim characterized the dyslipidemia prevalence in FAs and major ethnic subgroups using nationally representative NHANES data. FAs had the highest rates of elevated triglycerides. Particularly, middle-aged FA adults had the highest rates of elevated triglycerides, TC, and overall dyslipidemia compared to other ethnic groups. The lipid profiles of FA men was worse than FA women as well as men from other ethnic groups for all though FAs generally demonstrated higher HDL-C levels. Secondly, we examined associations between uric acid (UA) levels and lipid profiles, adjusting genetic and non-genetic factors. 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. Furthermore, 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. Thirdly, we characterized the allele frequencies of genetic variants with PGx relevance, including statin exposure/response. 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. These distinct allele distributions indicate that FAs are more likely to require genotype-guided statins, based on their higher genetic risk for statin-related myopathy than other populations. This is the first application of the predesigned PGx (120-SNP) TaqMan® OpenArray® panel in FAs, though its design based on non-FAs may have limited detection of population-specific variants affecting statin response. 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.