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 affects response to clopidogrel. CYP2C19 loss-of-function alleles are associated with more cardiovascular events.[5] Concomitant proton pump inhibitors, which are also metabolized by CYP2C19, may[6][7] (especially inhibitors other than pantoprazole[8]) or may not[5][9][10] 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.[10]

External links

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. 5.0 5.1 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.
  6. 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.
  7. 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.
  8. 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
  9. 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.
  10. 10.0 10.1 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.