the clinical impact of cyp2c19 *2 and *3 polymorphism on clopidogrel and cost analysis

1
POSTER PRESENTATION Open Access The clinical impact of CYP2C19 *2 and *3 polymorphism on Clopidogrel and cost analysis Al Meman A * , Khalaf H, Rasool Seemab From 2nd International Genomic Medical Conference (IGMC 2013) Jeddah, Kingdom of Saudi Arabia. 24-27 November 2013 Background Inter individual variability to Clopidogrel response is well recognized as a strapping barrier in front of clinicians. It has been mentioned that the pharmacogenetic variations may explain 30-50 percent in this variability [1,2]. Several recent landmark studies have proven the importance of 2C19 genotyping in treatment using clopidogrel [1-3]. Therefore we sought to investigate the variability in PFT response to CYP2C19 polymorphism and compare it with the clinical presentation. Furthermore, cost analysis is considered. Materials and methods One hundred and seventy Saudi patients who were stable on 75 mg clopidogrel at least for one month for various cardiac indications were enrolled in Prince Sultan Cardiac Center, Buraidah. DNA was extracted by MagNAPure [LC,Roche, Germany].CYP2C19 Genotyping for *1, *2 and *3 was conducted by real-time PCR [Roche Molecular Bio- chemicals, Mannheim, Germany]. PFT was carried out by (Verify Now P2Y12) for all the patients. The clinical events were documented retrospectively for all patients. Results One hundred seventeen patients presented with the wild variant 1/1, 19 patients with 1/2, and 34 patients with 2/2. We couldnt detect allele 3. There is a significant associa- tion between different genotyping and the percentage of inhibition (P = 0.0002). 1/1 patients tend to be moderate to - extensive metabolizers, whereas the majority of the rest are slow metabolizers. One hundred twenty three patients presented with no symptoms. Interestingly, no association was found between the adequacy of the PFT and the clinical symptoms (P = 0.60) and PPIs did not affect the overall response. Furthermore, Aspirin dose didnt impact on the clinical symptoms (P = 0.080). The cost of doing the PFT is 250 SR/patient and 200 SR/ patient (real-time PCR) for kits and materials excluding equipment and labors. Conclusions Although the platelet function testing varied significantly with polymorphism, the clinical symptoms were not asso- ciated. The running cost is affordable if clinical association was found to be significant. Published: 2 April 2014 References 1. Mega JL, Close SL, Wiviott SD, et al: Cytochrome P-450 polymorphisms and response to clopidogrel. N Engl J Med 2009, 360:354-362. 2. Simon T, Verstuyft C, Mary-Krause M, et al: Genetic Determinants of Response to Clopidogrel and Cardiovascular Events. N Eng J Med 2009, 360:363-75. 3. Collet JP, Hulot JS, Pena A, et al: Cytochrome P450 2C19 polymorphism in young patients treated with clopidogrel after myocardial infarction: a cohort study. The Lancet 2009, 373(9660):309-317. doi:10.1186/1471-2164-15-S2-P19 Cite this article as: Meman A et al.: The clinical impact of CYP2C19 *2 and *3 polymorphism on Clopidogrel and cost analysis. BMC Genomics 2014 15(Suppl 2):P19. Submit your next manuscript to BioMed Central and take full advantage of: Convenient online submission Thorough peer review No space constraints or color figure charges Immediate publication on acceptance Inclusion in PubMed, CAS, Scopus and Google Scholar Research which is freely available for redistribution Submit your manuscript at www.biomedcentral.com/submit * Correspondence: [email protected] Intervention group at Prince Sultan Cardiac Center, Qassim & Genetic laboratory at Qassim University, Kingdom of Saudi Arabia Meman A et al. BMC Genomics 2014, 15(Suppl 2):P19 http://www.biomedcentral.com/1471-2164/15/S2/P19 © 2014 Al Meman et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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POSTER PRESENTATION Open Access

The clinical impact of CYP2C19 *2 and *3polymorphism on Clopidogrel and cost analysisAl Meman A*, Khalaf H, Rasool Seemab

From 2nd International Genomic Medical Conference (IGMC 2013)Jeddah, Kingdom of Saudi Arabia. 24-27 November 2013

BackgroundInter individual variability to Clopidogrel response is wellrecognized as a strapping barrier in front of clinicians. Ithas been mentioned that the pharmacogenetic variationsmay explain 30-50 percent in this variability [1,2]. Severalrecent landmark studies have proven the importance of2C19 genotyping in treatment using clopidogrel [1-3].Therefore we sought to investigate the variability in PFTresponse to CYP2C19 polymorphism and compare it withthe clinical presentation. Furthermore, cost analysis isconsidered.

Materials and methodsOne hundred and seventy Saudi patients who were stableon 75 mg clopidogrel at least for one month for variouscardiac indications were enrolled in Prince Sultan CardiacCenter, Buraidah. DNA was extracted by MagNAPure[LC,Roche, Germany].CYP2C19 Genotyping for *1, *2 and*3 was conducted by real-time PCR [Roche Molecular Bio-chemicals, Mannheim, Germany]. PFT was carried out by(Verify Now P2Y12) for all the patients. The clinical eventswere documented retrospectively for all patients.

ResultsOne hundred seventeen patients presented with the wildvariant 1/1, 19 patients with 1/2, and 34 patients with 2/2.We couldn’t detect allele 3. There is a significant associa-tion between different genotyping and the percentage ofinhibition (P = 0.0002). 1/1 patients tend to be moderateto - extensive metabolizers, whereas the majority of therest are slow metabolizers. One hundred twenty threepatients presented with no symptoms. Interestingly, noassociation was found between the adequacy of the PFTand the clinical symptoms (P = 0.60) and PPIs did not

affect the overall response. Furthermore, Aspirin dosedidn’t impact on the clinical symptoms (P = 0.080). Thecost of doing the PFT is 250 SR/patient and 200 SR/patient (real-time PCR) for kits and materials excludingequipment and labors.

ConclusionsAlthough the platelet function testing varied significantlywith polymorphism, the clinical symptoms were not asso-ciated. The running cost is affordable if clinical associationwas found to be significant.

Published: 2 April 2014

References1. Mega JL, Close SL, Wiviott SD, et al: Cytochrome P-450 polymorphisms

and response to clopidogrel. N Engl J Med 2009, 360:354-362.2. Simon T, Verstuyft C, Mary-Krause M, et al: Genetic Determinants of Response

to Clopidogrel and Cardiovascular Events. N Eng J Med 2009, 360:363-75.3. Collet JP, Hulot JS, Pena A, et al: Cytochrome P450 2C19 polymorphism in

young patients treated with clopidogrel after myocardial infarction: acohort study. The Lancet 2009, 373(9660):309-317.

doi:10.1186/1471-2164-15-S2-P19Cite this article as: Meman A et al.: The clinical impact of CYP2C19 *2and *3 polymorphism on Clopidogrel and cost analysis. BMC Genomics2014 15(Suppl 2):P19.

Submit your next manuscript to BioMed Centraland take full advantage of:

• Convenient online submission

• Thorough peer review

• No space constraints or color figure charges

• Immediate publication on acceptance

• Inclusion in PubMed, CAS, Scopus and Google Scholar

• Research which is freely available for redistribution

Submit your manuscript at www.biomedcentral.com/submit

* Correspondence: [email protected] group at Prince Sultan Cardiac Center, Qassim & Geneticlaboratory at Qassim University, Kingdom of Saudi Arabia

Meman A et al. BMC Genomics 2014, 15(Suppl 2):P19http://www.biomedcentral.com/1471-2164/15/S2/P19

© 2014 Al Meman et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the CreativeCommons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, andreproduction in any medium, provided the original work is properly cited.