Pharmacogenetic association study on clopidogrel response in Puerto Rican Hispanics with cardiovascular disease: a novel characterization of a Caribbean population

• Main Authors: Hernandez-Suarez DF, Botton MR, Scott SA, Tomey MI, Garcia MJ, Wiley J, Villablanca PA, Melin K, Lopez-Candales A, Renta JY, Duconge J
• Format: Article
• Language: English
• Published: Dove Medical Press 2018-06-01
• Series: Pharmacogenomics and Personalized Medicine
• Subjects: Clopidogrel; platelet reactivity; genotyping; Hispanics; Puerto Rico.
• Online Access: https://www.dovepress.com/pharmacogenetic-association-study-on-clopidogrel-response-in-puerto-ri-peer-reviewed-article-PGPM

Dagmar F Hernandez-Suarez,1 Mariana R Botton,2 Stuart A Scott,2 Matthew I Tomey,3 Mario J Garcia,4 Jose Wiley,4 Pedro A Villablanca,5 Kyle Melin,6 Angel Lopez-Candales,7 Jessicca Y Renta,8 Jorge Duconge9 1Cardiovascular Medicine Division, Department of Medicine, University of Puerto Rico School of Medicine, San Juan, PR, USA; 2Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA; 3Cardiovascular Medicine Division, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA; 4Division of Cardiovascular Diseases, Department of Medicine, Montefiore Medical Center/Albert Einstein College of Medicine New York, NY, USA; 5Division of Cardiology, Department of Medicine, New York University Langone Medical Center, New York, NY, USA; 6Department of Pharmacy Practice, University of Puerto Rico Medical Sciences Campus, San Juan, PR, USA; 7Cardiovascular Medicine Division, Department of Medicine, University of Puerto Rico School of Medicine, San Juan, PR, USA; 8Department of Biochemistry, University of Puerto Rico Medical Sciences Campus, San Juan, PR, USA; 9Pharmaceutical Sciences Department, University of Puerto Rico Medical Sciences Campus, San Juan, PR, USA 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. Keywords: clopidogrel, platelet reactivity, genotyping, Hispanics, Puerto Rico