Discovery of ancestry-specific variants associated with clopidogrel response among Caribbean Hispanics.

IF 4.7 2区医学 Q1 GENETICS & HEREDITY NPJ Genomic Medicine Pub Date : 2025-03-07 DOI:10.1038/s41525-025-00479-3

Guang Yang, Pablo González, Mariangeli Moneró, Kelvin Carrasquillo, Jessicca Y Renta, Dagmar F Hernandez-Suarez, Mariana R Botton, Kyle Melin, Stuart A Scott, Gualberto Ruaño, Abiel Roche-Lima, Cristina Alarcon, Marylyn D Ritchie, Minoli A Perera, Jorge Duconge

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Abstract

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.

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来源期刊

NPJ Genomic Medicine Biochemistry, Genetics and Molecular Biology-Molecular Biology

CiteScore

9.40

自引率

1.90%

发文量

审稿时长

17 weeks

期刊介绍： npj Genomic Medicine is an international, peer-reviewed journal dedicated to publishing the most important scientific advances in all aspects of genomics and its application in the practice of medicine. The journal defines genomic medicine as "diagnosis, prognosis, prevention and/or treatment of disease and disorders of the mind and body, using approaches informed or enabled by knowledge of the genome and the molecules it encodes." Relevant and high-impact papers that encompass studies of individuals, families, or populations are considered for publication. An emphasis will include coupling detailed phenotype and genome sequencing information, both enabled by new technologies and informatics, to delineate the underlying aetiology of disease. Clinical recommendations and/or guidelines of how that data should be used in the clinical management of those patients in the study, and others, are also encouraged.