RCMI-CCRHD Research Project 2017–2022 “Adopting a Precision Medicine Paradigm in Puerto Rico: leveraging ancestral diversity to identify predictors of clopidogrel response”

Research Areas

  • Precision Medicine (PM) and Pharmacogenomics (PGx)
  • Model-informed Precision Dosing (MIPD)
  • Pharmacokinetics/ Pharmacodynamics (PK/PD) Modeling and Pharmacometrics

Scientific Achievements

  • Developed and applied a genetic-based treatment guide for blood thinners in over 200 heart patients, discovery of new genetic variants in Hispanics that influence response to warfarin and clopidogrel (3 PhD students, 2 postdocs, >10 undergrads mentored; 2 Research Assistants).
  • Built tools that use genetic and computer-based models to help predict the best medication dose for each patient (e.g., Copyright Registration Certificate No. TXu 2-229-761).
  • Led the first-ever genomic study of medication response in Caribbean Hispanic patients (1 PhD student thesis).
  • Established a secure patient database (over 800 participants) and biobank

Funding

RCMI Funding:

  • NIH/NIMHD U54MD007600

Other funding obtained with RCMI support:

  • R01HG013773, NIH/NHGRI, “Social, Genomic, and Epigenomic Drivers of Clopidogrel Response”
  • R16GM149372, NIH/NIGMS, “Merging AI and Pharmacometrics to elucidate GDI linked to Clopidogrel”
  • SC1HL123911, NIH/NHLBI, “A Genomic Approach to Warfarin Dose Prescription in Admixed Hispanics”

Scientific Advance

Discovery of ancestry-specific variants associated with clopidogrel response among Caribbean Hispanics
Published in NPJ Genomic Medicine, Volume 10, 2025, PMCID: PMC11889249.
The study analyzed DNA from 511 Puerto Rican cardiovascular patients taking clopidogrel (a blood thinner) to learn why some patients don’t respond well to the drug. A genome-wide scan found genetic variants tied to high “on-treatment platelet reactivity” (meaning the drug is less effective). Signals in the CYP2C19 region appeared mainly in people with more European ancestry, while several other variants (including OSBPL10 rs1376606, DERL3 rs5030613, RGS6 rs9323567, and one in UNC5C) were also implicated. The findings highlight that drug-response genetics can differ by ancestry and that commonly used markers may not predict clopidogrel response as well in patients with higher non-European ancestry.
U54 GM133807 (NIGMS); U54 MD007600 (NIMHD/RCMI); 1U54 MD010723 (NIMHD); R25 GM061838 (NIGMS).
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