Association of CYP2C19*2 polymorphism with clopidogrel resistance among patients with high cardiovascular risk in Northeastern Mexico

Félix R. Cedillo-Salazar, Lizeth Martínez-Jacobo, Yadira X. Pérez-Páramo, Ricardo Cerda-Flores, Laura E. Martínez, José C. Jaime-Pérez, María G. Moreno-Treviño, Edelmiro Pérez-Rodríguez, Francisco J. Bosques-Padilla, Montserrat Cedillo-Avila, María A. Cedillo-Avila, Michelle Zamudio-Osuna

Research output: Contribution to journalArticle

Abstract

Objective: Oral antiplatelet drugs are a key to modern pharmacotherapy in cardiovascular atherothrombotic diseases. Clopidogrel (CLO) constitutes the main preventive treatment of atherothrombosis. However, a considerable inter-individual variation in CLO response has been documented, resulting in suboptimal therapy and an increased risk of recurrent adverse effects in some patients. The enzyme CYP2C19 has been reported to be the CYP isoform that activates CLO to its active metabolite. Several single nucleotide polymorphisms in the CYP2C19 gene have been identified as strong predictors of CLO-impaired pharmacological response. At least 16 variants have been associated with changes in CYP2C19 activity. Materials and Methods: The following research was composed of a total of 102 subjects with high cardiovascular risk in the northeast of Mexico, with a maintenance dose of 75 mg of CLO per day. The platelet reactivity was measured with VerifyNow P2Y12 assay, while the presence of CYP2C19*2 was identified by real-time polymerase chain reaction. Results: Patients were categorized by CYP2C19 metabolizer status based on *2 genotypes using the common consensus star allele nomenclature as normal metabolizer (G/G), intermediate metabolizer (G/A), and poor metabolizer (A/A), respectively. The phenotype frequency for CYP2C19*2 was 74.5% (G/G), 21.6% (G/A), and 3.9% (A/A). The subjects with the A allele presented ≥235 P2Y12 reaction unit levels, classifying them how poor metabolizer. The prevalence of reduced CLO effectiveness was associated with the presence of CYP2C19*2 polymorphism among Mexican patients. Conclusion: The presence of the CYP2C19*2 allele is related to resistance to the antiplatelet effect of CLO (p = 0.003).

Original languageEnglish
Pages (from-to)324-329
Number of pages6
JournalArchivos de Cardiologia de Mexico
Volume89
Issue number4
DOIs
Publication statusPublished - 1 Jan 2019

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clopidogrel
Mexico
Alleles
Cytochrome P-450 CYP2C19
Platelet Aggregation Inhibitors
Terminology

All Science Journal Classification (ASJC) codes

  • Cardiology and Cardiovascular Medicine

Cite this

Cedillo-Salazar, F. R., Martínez-Jacobo, L., Pérez-Páramo, Y. X., Cerda-Flores, R., Martínez, L. E., Jaime-Pérez, J. C., ... Zamudio-Osuna, M. (2019). Association of CYP2C19*2 polymorphism with clopidogrel resistance among patients with high cardiovascular risk in Northeastern Mexico. Archivos de Cardiologia de Mexico, 89(4), 324-329. https://doi.org/10.24875/ACM.19000033
Cedillo-Salazar, Félix R. ; Martínez-Jacobo, Lizeth ; Pérez-Páramo, Yadira X. ; Cerda-Flores, Ricardo ; Martínez, Laura E. ; Jaime-Pérez, José C. ; Moreno-Treviño, María G. ; Pérez-Rodríguez, Edelmiro ; Bosques-Padilla, Francisco J. ; Cedillo-Avila, Montserrat ; Cedillo-Avila, María A. ; Zamudio-Osuna, Michelle. / Association of CYP2C19*2 polymorphism with clopidogrel resistance among patients with high cardiovascular risk in Northeastern Mexico. In: Archivos de Cardiologia de Mexico. 2019 ; Vol. 89, No. 4. pp. 324-329.
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abstract = "Objective: Oral antiplatelet drugs are a key to modern pharmacotherapy in cardiovascular atherothrombotic diseases. Clopidogrel (CLO) constitutes the main preventive treatment of atherothrombosis. However, a considerable inter-individual variation in CLO response has been documented, resulting in suboptimal therapy and an increased risk of recurrent adverse effects in some patients. The enzyme CYP2C19 has been reported to be the CYP isoform that activates CLO to its active metabolite. Several single nucleotide polymorphisms in the CYP2C19 gene have been identified as strong predictors of CLO-impaired pharmacological response. At least 16 variants have been associated with changes in CYP2C19 activity. Materials and Methods: The following research was composed of a total of 102 subjects with high cardiovascular risk in the northeast of Mexico, with a maintenance dose of 75 mg of CLO per day. The platelet reactivity was measured with VerifyNow P2Y12 assay, while the presence of CYP2C19*2 was identified by real-time polymerase chain reaction. Results: Patients were categorized by CYP2C19 metabolizer status based on *2 genotypes using the common consensus star allele nomenclature as normal metabolizer (G/G), intermediate metabolizer (G/A), and poor metabolizer (A/A), respectively. The phenotype frequency for CYP2C19*2 was 74.5{\%} (G/G), 21.6{\%} (G/A), and 3.9{\%} (A/A). The subjects with the A allele presented ≥235 P2Y12 reaction unit levels, classifying them how poor metabolizer. The prevalence of reduced CLO effectiveness was associated with the presence of CYP2C19*2 polymorphism among Mexican patients. Conclusion: The presence of the CYP2C19*2 allele is related to resistance to the antiplatelet effect of CLO (p = 0.003).",
author = "Cedillo-Salazar, {F{\'e}lix R.} and Lizeth Mart{\'i}nez-Jacobo and P{\'e}rez-P{\'a}ramo, {Yadira X.} and Ricardo Cerda-Flores and Mart{\'i}nez, {Laura E.} and Jaime-P{\'e}rez, {Jos{\'e} C.} and Moreno-Trevi{\~n}o, {Mar{\'i}a G.} and Edelmiro P{\'e}rez-Rodr{\'i}guez and Bosques-Padilla, {Francisco J.} and Montserrat Cedillo-Avila and Cedillo-Avila, {Mar{\'i}a A.} and Michelle Zamudio-Osuna",
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Cedillo-Salazar, FR, Martínez-Jacobo, L, Pérez-Páramo, YX, Cerda-Flores, R, Martínez, LE, Jaime-Pérez, JC, Moreno-Treviño, MG, Pérez-Rodríguez, E, Bosques-Padilla, FJ, Cedillo-Avila, M, Cedillo-Avila, MA & Zamudio-Osuna, M 2019, 'Association of CYP2C19*2 polymorphism with clopidogrel resistance among patients with high cardiovascular risk in Northeastern Mexico', Archivos de Cardiologia de Mexico, vol. 89, no. 4, pp. 324-329. https://doi.org/10.24875/ACM.19000033

Association of CYP2C19*2 polymorphism with clopidogrel resistance among patients with high cardiovascular risk in Northeastern Mexico. / Cedillo-Salazar, Félix R.; Martínez-Jacobo, Lizeth; Pérez-Páramo, Yadira X.; Cerda-Flores, Ricardo; Martínez, Laura E.; Jaime-Pérez, José C.; Moreno-Treviño, María G.; Pérez-Rodríguez, Edelmiro; Bosques-Padilla, Francisco J.; Cedillo-Avila, Montserrat; Cedillo-Avila, María A.; Zamudio-Osuna, Michelle.

In: Archivos de Cardiologia de Mexico, Vol. 89, No. 4, 01.01.2019, p. 324-329.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Association of CYP2C19*2 polymorphism with clopidogrel resistance among patients with high cardiovascular risk in Northeastern Mexico

AU - Cedillo-Salazar, Félix R.

AU - Martínez-Jacobo, Lizeth

AU - Pérez-Páramo, Yadira X.

AU - Cerda-Flores, Ricardo

AU - Martínez, Laura E.

AU - Jaime-Pérez, José C.

AU - Moreno-Treviño, María G.

AU - Pérez-Rodríguez, Edelmiro

AU - Bosques-Padilla, Francisco J.

AU - Cedillo-Avila, Montserrat

AU - Cedillo-Avila, María A.

AU - Zamudio-Osuna, Michelle

PY - 2019/1/1

Y1 - 2019/1/1

N2 - Objective: Oral antiplatelet drugs are a key to modern pharmacotherapy in cardiovascular atherothrombotic diseases. Clopidogrel (CLO) constitutes the main preventive treatment of atherothrombosis. However, a considerable inter-individual variation in CLO response has been documented, resulting in suboptimal therapy and an increased risk of recurrent adverse effects in some patients. The enzyme CYP2C19 has been reported to be the CYP isoform that activates CLO to its active metabolite. Several single nucleotide polymorphisms in the CYP2C19 gene have been identified as strong predictors of CLO-impaired pharmacological response. At least 16 variants have been associated with changes in CYP2C19 activity. Materials and Methods: The following research was composed of a total of 102 subjects with high cardiovascular risk in the northeast of Mexico, with a maintenance dose of 75 mg of CLO per day. The platelet reactivity was measured with VerifyNow P2Y12 assay, while the presence of CYP2C19*2 was identified by real-time polymerase chain reaction. Results: Patients were categorized by CYP2C19 metabolizer status based on *2 genotypes using the common consensus star allele nomenclature as normal metabolizer (G/G), intermediate metabolizer (G/A), and poor metabolizer (A/A), respectively. The phenotype frequency for CYP2C19*2 was 74.5% (G/G), 21.6% (G/A), and 3.9% (A/A). The subjects with the A allele presented ≥235 P2Y12 reaction unit levels, classifying them how poor metabolizer. The prevalence of reduced CLO effectiveness was associated with the presence of CYP2C19*2 polymorphism among Mexican patients. Conclusion: The presence of the CYP2C19*2 allele is related to resistance to the antiplatelet effect of CLO (p = 0.003).

AB - Objective: Oral antiplatelet drugs are a key to modern pharmacotherapy in cardiovascular atherothrombotic diseases. Clopidogrel (CLO) constitutes the main preventive treatment of atherothrombosis. However, a considerable inter-individual variation in CLO response has been documented, resulting in suboptimal therapy and an increased risk of recurrent adverse effects in some patients. The enzyme CYP2C19 has been reported to be the CYP isoform that activates CLO to its active metabolite. Several single nucleotide polymorphisms in the CYP2C19 gene have been identified as strong predictors of CLO-impaired pharmacological response. At least 16 variants have been associated with changes in CYP2C19 activity. Materials and Methods: The following research was composed of a total of 102 subjects with high cardiovascular risk in the northeast of Mexico, with a maintenance dose of 75 mg of CLO per day. The platelet reactivity was measured with VerifyNow P2Y12 assay, while the presence of CYP2C19*2 was identified by real-time polymerase chain reaction. Results: Patients were categorized by CYP2C19 metabolizer status based on *2 genotypes using the common consensus star allele nomenclature as normal metabolizer (G/G), intermediate metabolizer (G/A), and poor metabolizer (A/A), respectively. The phenotype frequency for CYP2C19*2 was 74.5% (G/G), 21.6% (G/A), and 3.9% (A/A). The subjects with the A allele presented ≥235 P2Y12 reaction unit levels, classifying them how poor metabolizer. The prevalence of reduced CLO effectiveness was associated with the presence of CYP2C19*2 polymorphism among Mexican patients. Conclusion: The presence of the CYP2C19*2 allele is related to resistance to the antiplatelet effect of CLO (p = 0.003).

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