Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

Clinical relevant polymorphisms affecting clopidogrel pharmacokinetics and pharmacodynamics: Insights from the Puerto Rico Newborn Screening Program

Dagmar Fredy Hernandez-Suarez
* ORCID logo ,
Jonnalie Tomassini-Fernandini
,
Angelica Cuevas
,
Anyelis Rosario-Berrios
,
Héctor Nuñez-Medina
,
Dariana Padilla-Arroyo
,
Nannette Rivera
,
Jennifer Liriano
,
Rocio Vega-Roman
,
Jessicca Renta
,
Kyle Melin
,
Jorge Duconge
ORCID logo
Version 1 : Received: 5 April 2018 / Approved: 6 April 2018 / Online: 6 April 2018 (11:31:00 CEST)

A peer-reviewed article of this Preprint also exists.

Hernandez-Suarez, D.F.; Tomassini-Fernandini, J.C.; Cuevas, A.; Rosario-Berrios, A.N.; Nuñez-Medina, H.J.; Padilla-Arroyo, D.; Rivera, N.; Liriano, J.; Vega-Roman, R.K.; Renta, J.Y.; Melin, K.; Duconge, J. Clinical Relevant Polymorphisms Affecting Clopidogrel Pharmacokinetics and Pharmacodynamics: Insights from the Puerto Rico Newborn Screening Program. Int. J. Environ. Res. Public Health 2018, 15, 1115. Hernandez-Suarez, D.F.; Tomassini-Fernandini, J.C.; Cuevas, A.; Rosario-Berrios, A.N.; Nuñez-Medina, H.J.; Padilla-Arroyo, D.; Rivera, N.; Liriano, J.; Vega-Roman, R.K.; Renta, J.Y.; Melin, K.; Duconge, J. Clinical Relevant Polymorphisms Affecting Clopidogrel Pharmacokinetics and Pharmacodynamics: Insights from the Puerto Rico Newborn Screening Program. Int. J. Environ. Res. Public Health 2018, 15, 1115.

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 1,000 Genome project, except for the Yoruba in Ibadan from Nigeria (YRI, West-African ancestry; 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

Subject

Medicine and Pharmacology, Cardiac and Cardiovascular Systems

Copyright: This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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