Clinical Relevant Polymorphisms Affecting Clopidogrel Pharmacokinetics and Pharmacodynamics: Insights from the Puerto Rico Newborn Screening Program

Dagmar F. Hernandez-Suarez, Jonnalie C. Tomassini-Fernandini, Angelica Cuevas, Anyelis N. Rosario-Berrios, Héctor J. Nuñez-Medina, Dariana Padilla-Arroyo, Nannette Rivera, Jennifer Liriano, Rocio K. Vega-Roman, Jessicca Y. Renta, Kyle Melin and Jorge Duconge
Additional contact information
Dagmar F. Hernandez-Suarez: Division of Cardiovascular Medicine, School of Medicine, University of Puerto Rico Medicine Sciences Campus, P.O. Box 365067, San Juan, PR 00936-5067, USA
Jonnalie C. Tomassini-Fernandini: Department of Biology, Natural Sciences, University of Puerto Rico Rio Piedras Campus, San Juan, PR 00931, USA
Angelica Cuevas: Department of Biology, Natural Sciences, University of Puerto Rico Rio Piedras Campus, San Juan, PR 00931, USA
Anyelis N. Rosario-Berrios: Department of Biology, Natural Sciences, University of Puerto Rico Rio Piedras Campus, San Juan, PR 00931, USA
Héctor J. Nuñez-Medina: Division of Cardiovascular Medicine, School of Medicine, University of Puerto Rico Medicine Sciences Campus, P.O. Box 365067, San Juan, PR 00936-5067, USA
Dariana Padilla-Arroyo: Pharmaceutical Sciences Department, University of Puerto Rico Medical Sciences Campus, San Juan, PR 00936, USA
Nannette Rivera: Department of Biology, Natural Sciences, University of Puerto Rico Rio Piedras Campus, San Juan, PR 00931, USA
Jennifer Liriano: Department of Biology, Natural Sciences, University of Puerto Rico Rio Piedras Campus, San Juan, PR 00931, USA
Rocio K. Vega-Roman: Department of Biology, Natural Sciences, University of Puerto Rico Bayamon Campus, Bayamon, PR 00959, USA
Jessicca Y. Renta: Department of Biochemistry, University of Puerto Rico Medical Sciences Campus, San Juan, PR 00936, USA
Kyle Melin: Department of Pharmacy Practice, University of Puerto Rico Medical Sciences Campus, San Juan, PR 00936, USA
Jorge Duconge: Pharmaceutical Sciences Department, University of Puerto Rico Medical Sciences Campus, San Juan, PR 00936, USA

IJERPH, 2018, vol. 15, issue 6, 1-13

Abstract: Background: Variations in several clopidogrel-pharmacogenes have been linked to clopidogrel response variability and clinical outcomes. We aimed to determine the frequency distribution of major polymorphisms on CYP2C19 , PON1 , ABCB1 and P2RY12 pharmacogenes in Puerto Ricans. Methods : This was a cross-sectional, population-based study of 200 unrelated “Guthrie” cards specimens from newborns registered in the Puerto Rican newborn screening program (PRNSP) between 2004 and 2014. Taqman ® SNP assay techniques were used for genotyping. Results: Minor allele frequencies (MAF) were 46% for PON1 (rs662), 41% for ABCB1 (rs1045642), 14% for CYP2C19 *17, 13% for CYP2C19 *2, 12% for P2RY12 -H2 and 0.3% for CYP2C19 *4. No carriers of the CYP2C19 *3 variants were detected. All alleles and genotype proportions were found to be in Hardy–Weinberg equilibrium (HWE). Overall, there were no significant differences between MAFs of these variants in Puerto Ricans and the general population ( n = 453) of the 1000 Genome project, except when comparisons to each individual parental group were performed (i.e., Africans, Europeans and East-Asians; p < 0.05). As expected, the prevalence of these markers in Puerto Ricans most resembled those in the 181 subjects from reference populations of the Americas. Conclusions: These prevalence data provide a necessary groundwork for future clinical studies of clopidogrel pharmacogenetics in Caribbean Hispanics.

Keywords: clopidogrel; pharmacogenetics; Puerto Ricans; genotypes; allele frequency (search for similar items in EconPapers)
JEL-codes: I I1 I3 Q Q5 (search for similar items in EconPapers)
Date: 2018
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