Cytochrome P-450: Difference between revisions
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** mean reduction was in warfarin dose was 1.92 mg (37% reduction) | ** mean reduction was in warfarin dose was 1.92 mg (37% reduction) | ||
** relative bleeding risk was 1.77 | ** relative bleeding risk was 1.77 | ||
===CYP2D6=== | |||
3-10% of anglos are poor metabolizers of drugs that use the CYP2D6 [[isoenzyme]].<ref name="pmid11710893">{{cite journal |author=Phillips KA, Veenstra DL, Oren E, Lee JK, Sadee W |title=Potential role of pharmacogenomics in reducing adverse drug reactions: a systematic review |journal=JAMA |volume=286 |issue=18 |pages=2270–9 |year=2001 |month=November |pmid=11710893 |doi= |url=http://jama.ama-assn.org/cgi/pmidlookup?view=long&pmid=11710893 |issn=}}</ref> This affects [[antidepressant]]s. | |||
==References== | ==References== | ||
<references/> | <references/> | ||
Revision as of 16:20, 19 June 2008
Cytochrome P-450 is a "superfamily of hundreds of closely related hemeproteins found throughout the phylogenetic spectrum, from animals, plants, fungi, to bacteria. They include numerous complex monooxygenases (mixed function oxygenases). In animals, these P-450 enzymes serve two major functions: (1) biosynthesis of steroids, fatty acids, and bile acids; (2) metabolism of endogenous and a wide variety of exogenous substrates, such as toxins and drugs (biotransformation). They are classified, according to their sequence similarities rather than functions, into CYP gene families (>40% homology) and subfamilies (>59% homology). For example, enzymes from the CYP1, CYP2, and CYP3 gene families are responsible for most drug metabolism."[1]
Common abnormal alleles
CYP2C9
CYP2C9 is an isoenzyme of cytochrome P-450. Polymorphisms of CYP2C9 explain 10% of variation in warfarin dosing[2], mainly among Caucasian patients as these variants are rare in African American and most Asian populations.[3] A meta-analysis of mainly Caucasian patients found[3]:
- CYP2C9*2 allele:
- present in 12.2% of patients
- mean reduction was in warfarin dose was 0.85 mg (17% reduction)
- relative bleeding risk was 1.91
- CYP2C9*3 allele:
- present in 7.9% of patients
- mean reduction was in warfarin dose was 1.92 mg (37% reduction)
- relative bleeding risk was 1.77
CYP2D6
3-10% of anglos are poor metabolizers of drugs that use the CYP2D6 isoenzyme.[4] This affects antidepressants.
References
- ↑ Anonymous (2024), Cytochrome P-450 (English). Medical Subject Headings. U.S. National Library of Medicine.
- ↑ Wadelius M, Chen LY, Downes K, et al (2005). "Common VKORC1 and GGCX polymorphisms associated with warfarin dose". Pharmacogenomics J. 5 (4): 262-70. DOI:10.1038/sj.tpj.6500313. PMID 15883587. Research Blogging.
- ↑ 3.0 3.1 Sanderson S, Emery J, Higgins J (2005). "CYP2C9 gene variants, drug dose, and bleeding risk in warfarin-treated patients: a HuGEnet systematic review and meta-analysis". Genet. Med. 7 (2): 97-104. PMID 15714076. [e]
- ↑ 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]