TY - JOUR
T1 - Pharmacogenetic association study on clopidogrel response in Puerto Rican hispanics with cardiovascular disease
T2 - A novel characterization of a Caribbean population
AU - Hernandez-Suarez, Dagmar F.
AU - Botton, Mariana R.
AU - Scott, Stuart A.
AU - Tomey, Matthew I.
AU - Garcia, Mario J.
AU - Wiley, Jose
AU - Villablanca, Pedro A.
AU - Melin, Kyle
AU - Lopez-Candales, Angel
AU - Renta, Jessicca Y.
AU - Duconge, Jorge
N1 - Funding Information:
We want to acknowledge first the patients for voluntarily participating in this study. Also, we would like to acknowledge the staff members of the Preadmission/Admission Department and Public Relationships Office at the Cardiovascular Center of Puerto Rico and the Caribbean, as well as the Endovascular Department of the University of Puerto Rico School of Medicine for their support during the development of this study. This publication was partially supported by the National Institute on Minority Health and Health Disparities (NIMHD) of the National Institutes of Health (NIH) Award Numbers CCTRECD-R25MD007607, TL1TR001434, U54MD007587 and the Research Minority Institutions (RCMI) award # 8G12 MD007600. JD is supported in part by the SC1 grant # HL123911 from the National Heart, Lung, and Blood Institute (NHLBI) and the Research Minority Institutions (RCMI) award # 2U54MD00760031. SAS is supported in part by the NIGMS of the NIH, through grant K23GM104401.
Publisher Copyright:
© 2018 Hernandez-Suarez et al.
PY - 2018/6/8
Y1 - 2018/6/8
N2 - Introduction: High on-treatment platelet reactivity (HTPR) to clopidogrel imparts an increased risk for ischemic events in adults with coronary artery disease. Platelet reactivity varies with ethnicity and is influenced by both clinical and genetic variables; however, no clopidogrel pharmacogenetic studies with Puerto Rican patients have been reported. Therefore, we sought to identify clinical and genetic determinants of on-treatment platelet reactivity in a cohort of Puerto Rican patients with cardiovascular disease. Methods: We performed a retrospective study of 111 patients on 75 mg/day maintenance dose of clopidogrel. Patients were allocated into 2 groups: Group I, without HTPR; and Group II, with HTPR. Platelet function was measured ex vivo using the VerifyNow® P2Y12 assay and HTPR was defined as P2Y12 reaction units (PRU) ≥230. Genotyping testing was performed using Taqman Genotyping Assays. ® Results: The mean PRU across the cohort was 203±61 PRU (range 8–324), and 42 (38%) patients had HTPR. Multiple logistic regression showed that 27% of the total variation in PRU was explained by a history of diabetes mellitus, hematocrit, CYP2C19*2, and PON1 p.Q192R. Body mass index (odds ratio [OR]=1.15; 95% CI: 1.03–1.27), diabetes mellitus (OR=3.46; 95% CI: 1.05–11.43), hematocrit (OR=0.75; 95% CI: 0.65–0.87), and CYP2C19*2 (OR=4.44; 95% CI: 1.21–16.20) were the only independent predictors of HTPR. Conclusion: Moreover, we propose a predictive model to determine PRU values as measured by VerifyNow P2Y12 assay for the Puerto Rican Hispanic population. This model has the potential to identify Hispanic patients at higher risk for adverse events on clopidogrel.
AB - Introduction: High on-treatment platelet reactivity (HTPR) to clopidogrel imparts an increased risk for ischemic events in adults with coronary artery disease. Platelet reactivity varies with ethnicity and is influenced by both clinical and genetic variables; however, no clopidogrel pharmacogenetic studies with Puerto Rican patients have been reported. Therefore, we sought to identify clinical and genetic determinants of on-treatment platelet reactivity in a cohort of Puerto Rican patients with cardiovascular disease. Methods: We performed a retrospective study of 111 patients on 75 mg/day maintenance dose of clopidogrel. Patients were allocated into 2 groups: Group I, without HTPR; and Group II, with HTPR. Platelet function was measured ex vivo using the VerifyNow® P2Y12 assay and HTPR was defined as P2Y12 reaction units (PRU) ≥230. Genotyping testing was performed using Taqman Genotyping Assays. ® Results: The mean PRU across the cohort was 203±61 PRU (range 8–324), and 42 (38%) patients had HTPR. Multiple logistic regression showed that 27% of the total variation in PRU was explained by a history of diabetes mellitus, hematocrit, CYP2C19*2, and PON1 p.Q192R. Body mass index (odds ratio [OR]=1.15; 95% CI: 1.03–1.27), diabetes mellitus (OR=3.46; 95% CI: 1.05–11.43), hematocrit (OR=0.75; 95% CI: 0.65–0.87), and CYP2C19*2 (OR=4.44; 95% CI: 1.21–16.20) were the only independent predictors of HTPR. Conclusion: Moreover, we propose a predictive model to determine PRU values as measured by VerifyNow P2Y12 assay for the Puerto Rican Hispanic population. This model has the potential to identify Hispanic patients at higher risk for adverse events on clopidogrel.
KW - Clopidogrel
KW - Genotyping
KW - Hispanics
KW - Platelet reactivity
KW - Puerto Rico
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U2 - 10.2147/PGPM.S165805
DO - 10.2147/PGPM.S165805
M3 - Article
AN - SCOPUS:85057111383
VL - 11
SP - 95
EP - 106
JO - Pharmacogenomics and Personalized Medicine
JF - Pharmacogenomics and Personalized Medicine
SN - 1178-7066
ER -