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

被引：0

作者：

Yang, Guang ^{[1
]}

Gonzalez, Pablo ^{[2
]}

Monero, Mariangeli ^{[2
]}

Carrasquillo, Kelvin ^{[3
]}

Renta, Jessicca Y. ^{[3
]}

Hernandez-Suarez, Dagmar F. ^{[4
]}

Botton, Mariana R. ^{[5
]}

Melin, Kyle ^{[6
]}

Scott, Stuart A. ^{[7
]}

Ruano, Gualberto ^{[8
]}

Roche-Lima, Abiel ^{[3
]}

Alarcon, Cristina ^{[1
]}

Ritchie, Marylyn D. ^{[9
,10
]}

Perera, Minoli A. ^{[1
]}

Duconge, Jorge ^{[3
,11
]}

机构：

[1] Northwestern Univ, Ctr Pharmacogen, Feinberg Sch Med, Dept Pharmacol, Chicago, IL USA

[2] Univ Puerto Rico, Sch Med, Dept Pharmacol, Med Sci Campus, San Juan, PR USA

[3] Univ Puerto Rico, Res Ctr Minor Inst RCMI Program, Ctr Collaborat Res Hlth Dispar CCRHD, Acad Affairs Deanship, Med Sci Campus, San Juan, PR 00921 USA

[4] Florida Int Univ, Herbert Wertheim Coll Med, Dept Translat Med, Miami, FL USA

[5] Hosp Clin Porto Alegre, Transplant Immunol & Personalized Med Unit, Porto Alegre, Brazil

[6] Univ Puerto Rico, Sch Pharm, Dept Pharm Practice, Med Sci Campus, San Juan, PR USA

[7] Stanford Univ, Dept Pathol, Palo Alto, CA USA

[8] Hartford Hosp, Inst Living, Hartford, CT USA

[9] Univ Penn, Perelman Sch Med, Dept Genet, Philadelphia, PA USA

[10] Univ Penn, Inst Biomed Informat, Perelman Sch Med, Philadelphia, PA USA

[11] Univ Puerto Rico, Sch Pharm, Dept Pharmaceut Sci, Med Sci Campus, San Juan, PR 00921 USA

来源：

NPJ GENOMIC MEDICINE | 2025年 / 10卷 / 01期

关键词：

ANTIPLATELET THERAPY; LOCAL-ANCESTRY; GENETIC-LOCI; GENOME; GENOTYPE; IDENTIFICATION; DIVERSITY; DISEASE; PROTEIN; MODEL;

D O I：

10.1038/s41525-025-00479-3

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

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.

引用

页数：12