Cytochrome P450 2D6 (CYP2D6), a member of the cytochrome P450 mixed-function oxidase system, is one of the most important enzymes involved in the metabolism of xenobiotics in the body. Whilst CYP2D6 is involved in the oxidation of a wide range of substrates of all the CYPs, there is considerable variability in its expression in the liver. Image File history File links No higher resolution available. ... The Protein Data Bank (PDB) is a repository for 3-D structural data of proteins and nucleic acids. ... Hugo is a masculine name. ... The Entrez logo The Entrez Global Query Cross-Database Search System allows access to databases at the National Center for Biotechnology Information (NCBI) website. ... The Mendelian Inheritance in Man project is a database that catalogues all the known diseases with a genetic component, and - when possible - links them to the relevant genes in the human genome. ... The National Center for Biotechnology Information (NCBI) is part of the US National Library of Medicine (NLM), which is a branch of the US National Institutes of Health. ... Swiss-Prot is a curated biological database of protein sequences created in 1986 by Amos Bairoch during his PhD and developed by the Swiss Institute of Bioinformatics and the European Bioinformatics Institute. ... The Enzyme Commission number (EC number) is a numerical classification scheme for enzymes, based on the chemical reactions they catalyze. ... Short and long arms Chromosome. ... Chromosome 22 is one of the 23 pairs of chromosomes in humans. ... Cytochrome P450 Oxidase (CYP2E1) Cytochrome P450 oxidase (commonly abbreviated CYP) is a generic term for a large number of related, but distinct, oxidative enzymes (EC 1. ... A xenobiotic is a chemical which is found in an organism but which is not normally produced or expected to be present in it. ... Cytochrome P450 Oxidase (CYP2E1) Cytochrome P450 oxidase (commonly abbreviated CYP) is a generic term for a large number of related, but distinct, oxidative enzymes (EC 1. ...

Genotype/phenotype variability

CYP2D6 shows the largest phenotypical variability amongst the CYPs, largely due to genetic polymorphism. The genotype accounts for normal, reduced and non-existent CYP2D6 function in subjects. Individuals in the mollusk species Donax variabilis show diverse coloration and patterning in their phenotypes. ... For a non-technical introduction to the topic, please see Introduction to genetics. ... In biology, polymorphism can be defined as the occurrence in the same habitat of two or more forms of a trait in such frequencies that the rarer cannot be maintained by recurrent mutation alone. ... This article does not cite its references or sources. ...

The CYP2D6 function in any particular subject may be described as one of the following:

• extensive metaboliser - these subjects have normal or reduced CYP2D6 function
• poor metaboliser - these subjects have little or no CYP2D6 function
• ultrarapid metaboliser - these subjects have multiple copies of the CYP2D6 gene expressed, and therefore greater-than-normal CYP2D6 function

A patient's CYP2D6 phenotype is often clinically determined via the administration of debrisoquine (a selective CYP2D6 substrate) and subsequent plasma concentration assay of the debrisoquine metabolite (4-hydroxydebrisoquine). More recently, a "DNA microarray" has been developed, known as the AmpliChip, which allows the automated determination of a patient's CYP2D6 (or CYP2C19) genotype. For a non-technical introduction to the topic, see Introduction to Genetics. ... A metabolite is the product of metabolism. ... Example of an approximately 40,000 probe spotted oligo microarray with enlarged inset to show detail. ... AmpliChip CYP450 Test is a clinical test from Roche. ... Cytochrome P450 2C19 (abbreviated CYP2C19), a member of the cytochrome P450 mixed-function oxidase system, is involved in the metabolism of xenobiotics in the body. ...

Genetic basis of variability

The genetic basis for extensive and poor metaboliser variability is the CYP2D6 allele, located on chromosome 22. Subjects who possess certain allelic variants will show normal, decreased or no CYP2D6 function depending on the allele. For the hard rock band, see Allele (band). ... Chromosome 22 is one of the 23 pairs of chromosomes in humans. ...

Ethnic factors in variability

Ethnicity is a factor in the occurrence of CYP2D6 variability. The prevalence of CYP2D6 poor metabolizers is approximately 6-10% amongst white populations, but is lower in most other ethnic groups such as Asians (2%) ^[4]. In blacks, the frequency of poor metabolizers is greater than for whites (1.6% vs. 0.44%) ^[2]. The occurrence of CYP2D6 ultrarapid metabolisers appears to be greater amongst Middle Eastern and North African populations ^[3]. The term white people (also whites or white race) has been defined as being a member of a group or race characterized by light pigmentation of the skin and to a human group having light-colored skin, especially of European ancestry. ... The term Asian people[1] is strictly a demonym for people from Asia. ... A Masai man in Kenya Black people or blacks is a political, social or cultural classification of people. ... A map showing countries commonly considered to be part of the Middle East The Middle East is a region comprising the lands around the southern and eastern parts of the Mediterranean Sea, a territory that extends from the eastern Mediterranean Sea to the Persian Gulf. ...  Northern Africa (UN subregion)  geographic, including above North Africa or Northern Africa is the northernmost region of the African continent, generally divided politically from Sub-Saharan Africa. ...

This variability is accounted for by the differences in the prevalence of various CYP2D6 alleles amongst the populations - approximately 10% of whites appear to have the non-functional CYP2D6*4 allele^[1] while approximately 50% of Asians possess the CYP2D6*10 allele^[1], which should produce decreased CYP2D6 function; however this still appears to be within the normal range and are still grouped as extensive metabolisers.

CYP2D6 Ligands

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References

1. ^{a  b}  Comparison of three CYP2D6 probe substrates and genotype in Ghanaians, Chinese and Caucasians. Pharmacogenetics 1998 Aug; 8(4): 325-33. PMID 9731719
2. ^a  Gaedigk A, Bradford LD, Marcucci KA, Leeder JS (2002). "Unique CYP2D6 activity distribution and genotype-phenotype discordance in black Americans". Clinical Pharmacology & Therapeutics 72 (1): 76-89. PMID 12152006.  Fulltext options (subscription and/or purchase may or may not be required) List of Library Holdings Worldwide
3. ^a  Frequent occurrence of CYP2D6 gene duplication in Saudi Arabians. Pharmacogenetics 1997 Jun; 7(3): 187-91 PMID 9241658
4. ^a  Australian Medicines Handbook (AMH) 2004. ISBN 0-9578521-4-2

See also

• Caraco Y (2004). Genes and the response to drugs. New Engl J Med 351 (27), 2867-9. PMID 15625340

External links

• Flockhart Lab Cyp2D6 Substrates Page at IUPUI