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AccuType CP, Clopidrogrel CYP2C19 Genotype

AccuType CP, Clopidrogrel CYP2C19 Genotype

Test Highlight

AccuType® CP, Clopidogrel CYP2C19 Genotype

  

Clinical Use

  • Assess likelihood of reduced or enhanced clopidogrel response in cardiovascular patients

  • Guide treatment strategy for patients being considered for or receiving clopidogrel therapy

Clinical Background

Clopidogrel (Plavix®) is widely used to treat patients who have had a previous cardiovascular event and to prevent stent thrombosis following stent implantation. Response to this antiplatelet drug is affected by drug absorption and activation, concomitant medications (eg, omeprazole), obesity, insulin resistance, and patient adherence to the therapy.1,2

Genetic variations in the CYP2C19 gene substantially reduce or enhance clopidogrel metabolism to its active form. Reduced-function alleles have been reported in 26% of Caucasians, 32% of Africans, and >55% of East Asians.3,4 Intermediate and poor metabolizers have either 1 or 2 reduced-function CYP2C19 alleles (*2, *3, *4, etc), resulting in lower levels of active drug and a reduced antiplatelet response to clopidogrel.2,5 In the majority of studies, patients with reduced-function alleles have a relatively increased risk of recurrent cardiovascular events and stent thrombosis;2,5-7 however, one study of mostly non-stented patients did not show such an increase in cardiovascular event rate.8

An enhanced-function allele (CYP2C19*17) has been reported in 39% of Caucasians, 37% of Ethiopians, and 2% of East Asians.3,9 Some, but not all, studies show that carriers of the CYP2C19*17 allele experience an enhanced antiplatelet response to clopidogrel, a lower cardiovascular event rate, and an increased bleeding risk relative to non-carriers.5,6,10

The laboratory-developed AccuType CP test can be used to identify intermediate and poor metabolizers who may have a reduced response to clopidogrel, as well as hyperextensive (ultra-rapid) metabolizers who may have an enhanced response to clopidogrel. A suggested strategy for using test results is shown in the Figure.
Figure. Suggested use of CYP2C19 genotype test results. 2,5,11

Method

Selected exons of the CYP2C19 gene are amplified by multiplex polymerase chain reaction followed by single nucleotide primer extension and detection using an automated DNA sequencer. Results are reported as CYP2C19 genotype and metabolizer phenotype.

Interpretive Information

See Clinical Background and Figure. Additional assistance in interpreting results is available from our Genetic Counselors by calling 1-866-GENE-INFO (1-866-436-3463).

References

  1. Toth PP, Armani A. Thienopyridine therapy and risk for cardiovascular events in secondary prevention. Curr Atheroscler Rep. 2009;11:364-370.

  2. Simon T, Verstuyft C, Mary-Krause M, et al. Genetic determinants of response to clopidogrel and cardiovascular events. N Engl J Med. 2009;360:363-375.

  3. Myrand SP, Sekiguchi K, Man MZ, et al. Pharmacokinetics/genotype associations for major cytochrome P450 enzymes in native and first- and third-generation Japanese populations: comparison with Korean, Chinese, and Caucasian populations. Clin Pharmacol Ther. 2008;84:347-361.

  4. Dandara C, Masimirembwa CM, Magimba A, et al. Genetic polymorphism of CYP2D6 and CYP2C19 in east- and southern African populations including psychiatric patients. Eur J Clin Pharmacol. 2001;57:11-17.

  5. Mega JL, Close SL, Wiviott SD, et al. Cytochrome P-450 polymorphisms and response to clopidogrel. N Engl J Med. 2009;360:354-362.

  6. Wallentin L, James S, Storey RF, et al. Effect of CYP2C19 and ABCB1 single nucleotide polymorphisms on outcomes of treatment with ticagrelor versus clopidogrel for acute coronary syndromes: a genetic substudy of the PLATO trial. Lancet. 2010;376:1320-1328.

  7. Hulot JS, Collet JP, Silvain J, et al. Cardiovascular risk in clopidogrel-treated patients according to cytochrome P450 2C19*2 loss-of-function allele or proton pump inhibitor coadministration: a systematic meta-analysis. J Am Coll Cardiol. 2010;56:134-143.

  8. Pare G, Shamir RM, Yusuf S, et al. Effects of CYP2C19 genotype on outcomes of clopidogrel treatment. N Engl J Med. 2010;363:1704-1714.

  9. Sim SC, Risinger C, Dahl ML, et al. A common novel CYP2C19 gene variant causes ultrarapid drug metabolism relevant for the drug response to proton pump inhibitors and antidepressants. Clin Pharmacol Ther. 2006;79:103-113.

  10. Sibbing D, Koch W, Gebhard D, et al. Cytochrome 2C19*17 allelic variant, platelet aggregation, bleeding events, and stent thrombosis in clopidogrel-treated patients with coronary stent placement. Circulation. 2010;121:512-518.

  11. Gladding P, White H, Voss J, et al. Pharmacogenetic testing for clopidogrel using the RAPID INFINITI analyzer. JACC Cardiovasc Interv. 2009;2:1095-1101.
     

This test was developed and its performance characteristics have been determined by Quest Diagnostics Nichols Institute. Performance characteristics refer to the analytical performance of the test.

Content reviewed 12/2012
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