Cytochrome P-450 CYP2C19

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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

  1. Online Mendelian Inheritance in Man, OMIM®. Johns Hopkins University, Baltimore, MD. MIM Number: 124020. World Wide Web URL: http://omim.org/.
  2. Phillips KA, Veenstra DL, Oren E, Lee JK, Sadee W (November 2001). "Potential role of pharmacogenomics in reducing adverse drug reactions: a systematic review". JAMA 286 (18): 2270–9. PMID 11710893[e]
  3. Weinshilboum R (February 2003). "Inheritance and drug response". N. Engl. J. Med. 348 (6): 529–37. DOI:10.1056/NEJMra020021. PMID 12571261. Research Blogging.
  4. 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.
  5. 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. 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.
  7. 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.
  8. 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.
  9. 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
  10. 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. 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.
  12. 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.