Discovery of ancestry-specific variants associated with clopidogrel response among Caribbean Hispanics
High on-treatment platelet reactivity (HTPR) with clopidogrel predicts ischemic events in adults with coronary artery disease, and while HTPR varies by ethnicity, no genome-wide association study (GWAS) of clopidogrel response has been conducted in Caribbean Hispanics. This study aimed to identify genetic predictors of HTPR in a cohort of 511 Puerto Rican cardiovascular patients treated with clopidogrel, stratified by P2Y12 reaction units (PRU) into responders and non-responders (HTPR). Local ancestry inference (LAI) and traditional GWAS identified variants in the CYP2C19 region associated with HTPR, primarily in individuals with European ancestry. Three variants (OSBPL10 rs1376606, DERL3 rs5030613, RGS6 rs9323567) showed suggestive significance, and a variant in UNC5C was linked to increased HTPR risk. These findings highlight the unique genetic landscape of Caribbean Hispanics and challenge the significance of CYP2C19*2 in predicting clopidogrel response in patients with high non-European ancestry. Further studies are needed to replicate these results in other diverse cohorts.
Authors
- Jorgé Duconge (ORCID: https://orcid.org/0000-0002-5955-3449)
- Gualberto Ruaño (ORCID: https://orcid.org/0000-0002-5348-4702)
- Abiel Roche-Lima (ORCID: https://orcid.org/0000-0003-2246-6744)
- Mariana Rodrigues Botton (ORCID: https://orcid.org/0000-0002-0509-9199)
- Mariangeli Moneró
- Minoli A. Perera (ORCID: https://orcid.org/0000-0002-1146-2791)
- Jessicca Y. Renta (ORCID: https://orcid.org/0000-0002-5255-7834)
- Guang Yang (ORCID: https://orcid.org/0000-0003-2920-6523)
- Dagmar F. Hernández-Suárez (ORCID: https://orcid.org/0000-0003-1850-9078)
- Kyle Melín (ORCID: https://orcid.org/0000-0002-4698-8021)
- Stuart A. Scott (ORCID: https://orcid.org/0000-0001-5720-1864)
- Kelvin Carrasquillo (ORCID: https://orcid.org/0000-0001-7224-2349)
- Marylyn DeRiggi Ritchie (ORCID: https://orcid.org/0000-0002-1208-1720)
- Pablo González (ORCID: https://orcid.org/0000-0001-5512-5757)
- Cristina Alarcón (ORCID: https://orcid.org/0009-0003-0872-9904)
Institutions
- Northwestern University (US)
- Hartford Hospital (US)
- University of Puerto Rico, Medical Sciences Campus (PR)
- Palo Alto University (US)
- Florida International University (US)
- Hospital de Clínicas de Porto Alegre (BR)
- University of Pennsylvania (US)
- Stanford University (US)
Publication Details
- Journal
- npj Genomic Medicine
- Published
- 2025-03-07
- DOI
- https://doi.org/10.1038/s41525-025-00479-3
- Citations
- 3
- Primary Topic
- Antiplatelet Therapy and Cardiovascular Diseases
- Type
- article
- Field-Weighted Citation Impact
- 4.16
Funders
- Universidade Federal do Rio Grande do Sul
- National Institutes of Health
- National Institute of General Medical Sciences
- National Institute of Allergy and Infectious Diseases
- National Institute on Minority Health and Health Disparities