Cytochrome P-450 CYP2C19
In biology, the cytochrome P-450 CYP2D19 is an isoenzyme of cytochrome P-450.[1] 2-6% of anglos and 15-25% of asians are poor metabolizers of drugs that use the CYP2C19 isoenzyme.[2][3] More recently, a study suggests that 30% of patients may have a reduced-function allele with the reduced function allele being more common in asians and africans and less common in anglos and hispanics.[4]
CYP2C19 polymorphism may affect response to clopidogrel. A systematic review of association studies concluded CYP2C19 "genetic association studies does not indicate a substantial or consistent influence of CYP2C19 gene polymorphisms on the clinical efficacy of clopidogrel."[5] Prior studies were conflicting whether loss-of-function alleles are associated with more cardiovascular events. Concomitant proton pump inhibitors, which are also metabolized by CYP2C19, may[6][7][8] (especially inhibitors other than pantoprazole[9]) or may not[6][10][11] increase adverse cardiac events.
In one negative analysis, adding PPIs to clopidogrel as associated with increased adverse events, but not more so than adding PPIs to patients not taking clopidogrel.[11]
Beside testing for the CYP2C19*2 allele may reduce the occurrence of patients with high on-treatment platelet reactivity.[12]
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References
- ↑ Online Mendelian Inheritance in Man, OMIM®. Johns Hopkins University, Baltimore, MD. MIM Number: 124020. World Wide Web URL: http://omim.org/.
- ↑ Phillips KA, Veenstra DL, Oren E, Lee JK, Sadee W (November 2001). "Potential role of pharmacogenomics in reducing drug-related side effects and adverse reactionss: a systematic review". JAMA 286 (18): 2270–9. PMID 11710893. [e]
- ↑ Weinshilboum R (February 2003). "Inheritance and drug response". N. Engl. J. Med. 348 (6): 529–37. DOI:10.1056/NEJMra020021. PMID 12571261. Research Blogging.
- ↑ Mega JL, Close SL, Wiviott SD, et al (December 2008). "Cytochrome P-450 Polymorphisms and Response to Clopidogrel". N. Engl. J. Med.. DOI:10.1056/NEJMoa0809171. PMID 19106084. Research Blogging.
- ↑ Bauer T, Bouman HJ, van Werkum JW, Ford NF, ten Berg JM, Taubert D (2011). "Impact of CYP2C19 variant genotypes on clinical efficacy of antiplatelet treatment with clopidogrel: systematic review and meta-analysis.". BMJ 343: d4588. DOI:10.1136/bmj.d4588. PMID 21816733. PMC PMC3191560. Research Blogging. Review in: Ann Intern Med. 2011 Dec 20;155(12):JC6-13
- ↑ 6.0 6.1 Simon T, Verstuyft C, Mary-Krause M, et al. (January 2009). "Genetic determinants of response to clopidogrel and cardiovascular events". N. Engl. J. Med. 360 (4): 363–75. DOI:10.1056/NEJMoa0808227. PMID 19106083. Research Blogging.
- ↑ Ho PM, Maddox TM, Wang L, et al. (March 2009). "Risk of adverse outcomes associated with concomitant use of clopidogrel and proton pump inhibitors following acute coronary syndrome". JAMA 301 (9): 937–44. DOI:10.1001/jama.2009.261. PMID 19258584. Research Blogging.
- ↑ Mega JL, Simon T, Collet JP, Anderson JL, Antman EM, Bliden K et al. (2010). "Reduced-function CYP2C19 genotype and risk of adverse clinical outcomes among patients treated with clopidogrel predominantly for PCI: a meta-analysis.". JAMA 304 (16): 1821-30. DOI:10.1001/jama.2010.1543. PMID 20978260. Research Blogging.
- ↑ Juurlink DN, Gomes T, Ko DT, Szmitko PE, Austin PC, Tu JV, Henry DA, Kopp A, Mamdani MM. A population-based study of the drug interaction between proton pump inhibitors and clopidogrel. CMAJ. 2009 Mar 31;180(7):713-8. Epub 2009 Jan 28. PMID 19176635
- ↑ Paré G, Mehta SR, Yusuf S, Anand SS, Connolly SJ, Hirsh J et al. (2010). "Effects of CYP2C19 genotype on outcomes of clopidogrel treatment.". N Engl J Med 363 (18): 1704-14. DOI:10.1056/NEJMoa1008410. PMID 20979470. Research Blogging.
- ↑ 11.0 11.1 Charlot M, Ahlehoff O, Norgaard ML, Jørgensen CH, Sørensen R, Abildstrøm SZ et al. (2010). "Proton-pump inhibitors are associated with increased cardiovascular risk independent of clopidogrel use: a nationwide cohort study.". Ann Intern Med 153 (6): 378-86. DOI:10.1059/0003-4819-153-6-201009210-00005. PMID 20855802. Research Blogging.
- ↑ Roberts JD, Wells GA, Le May MR, Labinaz M, Glover C, Froeschl M et al. (2012). "Point-of-care genetic testing for personalisation of antiplatelet treatment (RAPID GENE): a prospective, randomised, proof-of-concept trial.". Lancet. DOI:10.1016/S0140-6736(12)60161-5. PMID 22464343. Research Blogging.