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.<ref>{{OMIM|601130}}</ref> [[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 | ||
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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 | ||
===CYP2C19=== | |||
CYP2C19 polymorphism affects response to [[clopidogrel]]. 30% of patients may have a reduced-function allele.<ref>{{OMIM|124020}}</ref><ref name="pmid19106084">{{cite journal |author=Mega JL, Close SL, Wiviott SD, ''et al'' |title=Cytochrome P-450 Polymorphisms and Response to Clopidogrel |journal=N. Engl. J. Med. |volume= |issue= |pages= |year=2008 |month=December |pmid=19106084 |doi=10.1056/NEJMoa0809171 |url=http://content.nejm.org/cgi/pmidlookup?view=short&pmid=19106084&promo=ONFLNS19 |issn=}}</ref> | |||
===CYP2D6=== | ===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 many [[antidepressant]]s, [[metoprolol]] and other drugs that use this [[isoenzyme]]. More information is available at Entrez Gene.<ref name="urlGene Home">{{cite web |url=http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=1565 |title=Entrez Gene: CYP2D6 cytochrome P450, family 2, subfamily D, polypeptide 6 [ Homo sapiens ] |author=Anonymous |authorlink= |coauthors= |date= |format= |work= |publisher=National Library of Medicine |pages= |language= |archiveurl= |archivedate= |quote= |accessdate=2009-01-03 | 3-10% of anglos are poor metabolizers of drugs that use the CYP2D6 [[isoenzyme]].<ref>{{OMIM|124030}}</ref><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 many [[antidepressant]]s, [[metoprolol]] and other drugs that use this [[isoenzyme]]. More information is available at Entrez Gene.<ref name="urlGene Home">{{cite web |url=http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=1565 |title=Entrez Gene: CYP2D6 cytochrome P450, family 2, subfamily D, polypeptide 6 [ Homo sapiens ] |author=Anonymous |authorlink= |coauthors= |date= |format= |work= |publisher=National Library of Medicine |pages= |language= |archiveurl= |archivedate= |quote= |accessdate=2009-01-03}}</ref> | ||
==References== | ==References== | ||
Revision as of 22:17, 12 January 2009
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.[2] Polymorphisms of CYP2C9 explain 10% of variation in warfarin dosing[3], mainly among Caucasian patients as these variants are rare in African American and most Asian populations.[4] A meta-analysis of mainly Caucasian patients found[4]:
- 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
CYP2C19
CYP2C19 polymorphism affects response to clopidogrel. 30% of patients may have a reduced-function allele.[5][6]
CYP2D6
3-10% of anglos are poor metabolizers of drugs that use the CYP2D6 isoenzyme.[7][8] This affects many antidepressants, metoprolol and other drugs that use this isoenzyme. More information is available at Entrez Gene.[9]
References
- ↑ Anonymous (2024), Cytochrome P-450 (English). Medical Subject Headings. U.S. National Library of Medicine.
- ↑ Online Mendelian Inheritance in Man, OMIM®. Johns Hopkins University, Baltimore, MD. MIM Number: 601130. World Wide Web URL: http://omim.org/.
- ↑ 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.
- ↑ 4.0 4.1 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]
- ↑ Online Mendelian Inheritance in Man, OMIM®. Johns Hopkins University, Baltimore, MD. MIM Number: 124020. World Wide Web URL: http://omim.org/.
- ↑ 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.
- ↑ Online Mendelian Inheritance in Man, OMIM®. Johns Hopkins University, Baltimore, MD. MIM Number: 124030. 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 adverse drug reactions: a systematic review". JAMA 286 (18): 2270–9. PMID 11710893. [e]
- ↑ Anonymous. Entrez Gene: CYP2D6 cytochrome P450, family 2, subfamily D, polypeptide 6 [ Homo sapiens ]. National Library of Medicine. Retrieved on 2009-01-03.