The CYP2C19*1/*2 genotype does not adequately predict clopidogrel response in healthy malaysian volunteers

Yanti Nasyuhana Sani, Lim Sheau Chin, Lim Luen Hui, Nur Elyana Yazmin Mohd Redhuan Shah Edwin, Goh Teck Hwa, Victor L. Serebruany, Yuen Kah Hay

Research output: Contribution to journalArticle

Abstract

Background. The CYP2C19*2 allele may be associated with a reduced antiplatelet effect for clopidogrel. Here, we assessed whether CYP2C19*2 alleles correlate with clopidogrel responsiveness following the administration of clopidogrel in healthy Malaysian volunteers. Methods. Ninety volunteers were genotyped for CYP2C19*2 and CYP2C19*3 alleles. Forty-five of 90 volunteers were included in the clopidogrel response studies and triaged into three genotypes, namely, CYP2C19*1/*1 (n = 17), CYP2C19*1/ *2 (n = 21), and CYP2C19*2/*2 (n = 7). All subjects received 300 mg of clopidogrel, and platelet reactivity was assessed after a four-hour loading utilizing the VerifyNow-P2Y12 assay. Platelet activity was reported using P2Y12 reaction units (PRUs), and nonresponder status was prespecified at PRU ≥ 230. Results. Following clopidogrel intake, CYP2C19*2/*2 carriers had a significantly higher mean PRU compared to the CYP2C19*1/*2 and CYP2C19*1/*1 (291.0 ± 62.1 versus 232.5 ± 81.4 versus 147.4 ± 87.2 PRU, P <0.001) carriers. Almost half of the participants (46.7%) were found to be nonresponders (3 were CYP2C19*1/*1, 11 were CYP2C19*1/*2, and 7 were CYP2C19*2/*2). Conclusion. In healthy Malaysian volunteers, CYP2C19*2 allele was associated with a decrease in platelet responsiveness to clopidogrel. However, clopidogrel nonresponders can be found not only in the carriers of CYP2C19*2/*2, but also in the carriers of CYP2C19*1/*2 and CYP2C19*1/*1. The present paper demonstrated that genotype information does not correlate with clopidogrel response, and genotyping may represent a less robust approach compared to platelet activity testing in guiding clopidogrel therapy.

Original languageEnglish (US)
Article number128795
JournalCardiology Research and Practice
Volume1
Issue number1
DOIs
StatePublished - 2013

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clopidogrel
Healthy Volunteers
Genotype
Blood Platelets
Alleles
Cytochrome P-450 CYP2C19

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

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Nasyuhana Sani, Y., Sheau Chin, L., Luen Hui, L., Mohd Redhuan Shah Edwin, N. E. Y., Teck Hwa, G., Serebruany, V. L., & Kah Hay, Y. (2013). The CYP2C19*1/*2 genotype does not adequately predict clopidogrel response in healthy malaysian volunteers. Cardiology Research and Practice, 1(1), [128795]. https://doi.org/10.1155/2013/128795

The CYP2C19*1/*2 genotype does not adequately predict clopidogrel response in healthy malaysian volunteers. / Nasyuhana Sani, Yanti; Sheau Chin, Lim; Luen Hui, Lim; Mohd Redhuan Shah Edwin, Nur Elyana Yazmin; Teck Hwa, Goh; Serebruany, Victor L.; Kah Hay, Yuen.

In: Cardiology Research and Practice, Vol. 1, No. 1, 128795, 2013.

Research output: Contribution to journalArticle

Nasyuhana Sani, Y, Sheau Chin, L, Luen Hui, L, Mohd Redhuan Shah Edwin, NEY, Teck Hwa, G, Serebruany, VL & Kah Hay, Y 2013, 'The CYP2C19*1/*2 genotype does not adequately predict clopidogrel response in healthy malaysian volunteers', Cardiology Research and Practice, vol. 1, no. 1, 128795. https://doi.org/10.1155/2013/128795
Nasyuhana Sani Y, Sheau Chin L, Luen Hui L, Mohd Redhuan Shah Edwin NEY, Teck Hwa G, Serebruany VL et al. The CYP2C19*1/*2 genotype does not adequately predict clopidogrel response in healthy malaysian volunteers. Cardiology Research and Practice. 2013;1(1). 128795. https://doi.org/10.1155/2013/128795
Nasyuhana Sani, Yanti ; Sheau Chin, Lim ; Luen Hui, Lim ; Mohd Redhuan Shah Edwin, Nur Elyana Yazmin ; Teck Hwa, Goh ; Serebruany, Victor L. ; Kah Hay, Yuen. / The CYP2C19*1/*2 genotype does not adequately predict clopidogrel response in healthy malaysian volunteers. In: Cardiology Research and Practice. 2013 ; Vol. 1, No. 1.
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abstract = "Background. The CYP2C19*2 allele may be associated with a reduced antiplatelet effect for clopidogrel. Here, we assessed whether CYP2C19*2 alleles correlate with clopidogrel responsiveness following the administration of clopidogrel in healthy Malaysian volunteers. Methods. Ninety volunteers were genotyped for CYP2C19*2 and CYP2C19*3 alleles. Forty-five of 90 volunteers were included in the clopidogrel response studies and triaged into three genotypes, namely, CYP2C19*1/*1 (n = 17), CYP2C19*1/ *2 (n = 21), and CYP2C19*2/*2 (n = 7). All subjects received 300 mg of clopidogrel, and platelet reactivity was assessed after a four-hour loading utilizing the VerifyNow-P2Y12 assay. Platelet activity was reported using P2Y12 reaction units (PRUs), and nonresponder status was prespecified at PRU ≥ 230. Results. Following clopidogrel intake, CYP2C19*2/*2 carriers had a significantly higher mean PRU compared to the CYP2C19*1/*2 and CYP2C19*1/*1 (291.0 ± 62.1 versus 232.5 ± 81.4 versus 147.4 ± 87.2 PRU, P <0.001) carriers. Almost half of the participants (46.7{\%}) were found to be nonresponders (3 were CYP2C19*1/*1, 11 were CYP2C19*1/*2, and 7 were CYP2C19*2/*2). Conclusion. In healthy Malaysian volunteers, CYP2C19*2 allele was associated with a decrease in platelet responsiveness to clopidogrel. However, clopidogrel nonresponders can be found not only in the carriers of CYP2C19*2/*2, but also in the carriers of CYP2C19*1/*2 and CYP2C19*1/*1. The present paper demonstrated that genotype information does not correlate with clopidogrel response, and genotyping may represent a less robust approach compared to platelet activity testing in guiding clopidogrel therapy.",
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T1 - The CYP2C19*1/*2 genotype does not adequately predict clopidogrel response in healthy malaysian volunteers

AU - Nasyuhana Sani, Yanti

AU - Sheau Chin, Lim

AU - Luen Hui, Lim

AU - Mohd Redhuan Shah Edwin, Nur Elyana Yazmin

AU - Teck Hwa, Goh

AU - Serebruany, Victor L.

AU - Kah Hay, Yuen

PY - 2013

Y1 - 2013

N2 - Background. The CYP2C19*2 allele may be associated with a reduced antiplatelet effect for clopidogrel. Here, we assessed whether CYP2C19*2 alleles correlate with clopidogrel responsiveness following the administration of clopidogrel in healthy Malaysian volunteers. Methods. Ninety volunteers were genotyped for CYP2C19*2 and CYP2C19*3 alleles. Forty-five of 90 volunteers were included in the clopidogrel response studies and triaged into three genotypes, namely, CYP2C19*1/*1 (n = 17), CYP2C19*1/ *2 (n = 21), and CYP2C19*2/*2 (n = 7). All subjects received 300 mg of clopidogrel, and platelet reactivity was assessed after a four-hour loading utilizing the VerifyNow-P2Y12 assay. Platelet activity was reported using P2Y12 reaction units (PRUs), and nonresponder status was prespecified at PRU ≥ 230. Results. Following clopidogrel intake, CYP2C19*2/*2 carriers had a significantly higher mean PRU compared to the CYP2C19*1/*2 and CYP2C19*1/*1 (291.0 ± 62.1 versus 232.5 ± 81.4 versus 147.4 ± 87.2 PRU, P <0.001) carriers. Almost half of the participants (46.7%) were found to be nonresponders (3 were CYP2C19*1/*1, 11 were CYP2C19*1/*2, and 7 were CYP2C19*2/*2). Conclusion. In healthy Malaysian volunteers, CYP2C19*2 allele was associated with a decrease in platelet responsiveness to clopidogrel. However, clopidogrel nonresponders can be found not only in the carriers of CYP2C19*2/*2, but also in the carriers of CYP2C19*1/*2 and CYP2C19*1/*1. The present paper demonstrated that genotype information does not correlate with clopidogrel response, and genotyping may represent a less robust approach compared to platelet activity testing in guiding clopidogrel therapy.

AB - Background. The CYP2C19*2 allele may be associated with a reduced antiplatelet effect for clopidogrel. Here, we assessed whether CYP2C19*2 alleles correlate with clopidogrel responsiveness following the administration of clopidogrel in healthy Malaysian volunteers. Methods. Ninety volunteers were genotyped for CYP2C19*2 and CYP2C19*3 alleles. Forty-five of 90 volunteers were included in the clopidogrel response studies and triaged into three genotypes, namely, CYP2C19*1/*1 (n = 17), CYP2C19*1/ *2 (n = 21), and CYP2C19*2/*2 (n = 7). All subjects received 300 mg of clopidogrel, and platelet reactivity was assessed after a four-hour loading utilizing the VerifyNow-P2Y12 assay. Platelet activity was reported using P2Y12 reaction units (PRUs), and nonresponder status was prespecified at PRU ≥ 230. Results. Following clopidogrel intake, CYP2C19*2/*2 carriers had a significantly higher mean PRU compared to the CYP2C19*1/*2 and CYP2C19*1/*1 (291.0 ± 62.1 versus 232.5 ± 81.4 versus 147.4 ± 87.2 PRU, P <0.001) carriers. Almost half of the participants (46.7%) were found to be nonresponders (3 were CYP2C19*1/*1, 11 were CYP2C19*1/*2, and 7 were CYP2C19*2/*2). Conclusion. In healthy Malaysian volunteers, CYP2C19*2 allele was associated with a decrease in platelet responsiveness to clopidogrel. However, clopidogrel nonresponders can be found not only in the carriers of CYP2C19*2/*2, but also in the carriers of CYP2C19*1/*2 and CYP2C19*1/*1. The present paper demonstrated that genotype information does not correlate with clopidogrel response, and genotyping may represent a less robust approach compared to platelet activity testing in guiding clopidogrel therapy.

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