Cytochrome P-450: Difference between revisions
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==Common abnormal alleles== | ==Common abnormal alleles== | ||
===CYP2C9=== | ===CYP2C9=== | ||
''CYP2C9'' is an [[isoenzyme]] of cytochrome P-450. [[Genetic polymorphism|Polymorphisms]] of CYP2C9 explain 10% of variation in warfarin dosing<ref name="pmid15883587">{{cite journal |author=Wadelius M, Chen LY, Downes K, ''et al'' |title=Common VKORC1 and GGCX polymorphisms associated with warfarin dose |journal=Pharmacogenomics J. |volume=5 |issue=4 |pages=262-70 |year=2005 |pmid=15883587 |doi=10.1038/sj.tpj.6500313}}</ref>, mainly among Caucasian patients as these variants are rare in African American and most Asian populations.<ref name="pmid15714076">{{cite journal |author=Sanderson S, Emery J, Higgins J |title=CYP2C9 gene variants, drug dose, and bleeding risk in warfarin-treated patients: a HuGEnet systematic review and meta-analysis |journal=Genet. Med. |volume=7 |issue=2 |pages=97-104 |year=2005 |pmid=15714076 |doi=}}</ref> A [[meta-analysis]] of mainly Caucasian patients found<ref name="pmid15714076"/>: | ''CYP2C9'' is an [[isoenzyme]] of cytochrome P-450. [[Genetic polymorphism|Polymorphisms]] of CYP2C9 explain 10% of variation in [[warfarin]] dosing<ref name="pmid15883587">{{cite journal |author=Wadelius M, Chen LY, Downes K, ''et al'' |title=Common VKORC1 and GGCX polymorphisms associated with warfarin dose |journal=Pharmacogenomics J. |volume=5 |issue=4 |pages=262-70 |year=2005 |pmid=15883587 |doi=10.1038/sj.tpj.6500313}}</ref>, mainly among Caucasian patients as these variants are rare in African American and most Asian populations.<ref name="pmid15714076">{{cite journal |author=Sanderson S, Emery J, Higgins J |title=CYP2C9 gene variants, drug dose, and bleeding risk in warfarin-treated patients: a HuGEnet systematic review and meta-analysis |journal=Genet. Med. |volume=7 |issue=2 |pages=97-104 |year=2005 |pmid=15714076 |doi=}}</ref> A [[meta-analysis]] of mainly Caucasian patients found<ref name="pmid15714076"/>: | ||
* CYP2C9*2 allele: | * CYP2C9*2 allele: | ||
** present in 12.2% of patients | ** present in 12.2% of patients | ||
Revision as of 10:00, 21 May 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
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]