Genetic polymorphism of CYP2D6

Indian Journal of Pharmacology 01/2001; 33:147-169.

ABSTRACT CYP2D6 is polymorphically distributed and is responsible for the metabolism of several clinically important drugs. It is also related to several pathophysiological conditions. Defect alleles, causing poor metaboliser (PM) phenotype and alleles with duplicated or multiduplicated active genes, causing ultra extensive metabolism (UEM) have been described. CYP2D6 polymorphism exhibits pronounced interethnic variation. While initial observation and studies focused on population of Caucasian origin, later other populations also studied extensively. Differences in metabolism of drugs can lead to severe toxicity or therapeutic failure by altering the relation between dose and blood concentration of pharmacologically active drug or metabolite. Knowledge of individual's CYP2D6 status may be clinically and economically important and could provide the basis for a rational approach to drug prescription. Genetic polymorphism CYP2D6 pharmacogenetics KEY WORDS CYP 'CYP' is the abbreviation for cytochrome P-450, a subgroup of related enzymes or isoenzymes located in the endoplasmic reticulum and expressed mainly in the liver. It is also present in other organs, such as the intestine and the brain 4 . In mammals, most xenobiotics are metabolised via hepatic phase 1 metabolism by means of CYP monooxygenases 5 . Thirty or more different forms of these haem thiolate proteins have been characterized in humans 3 . The P450 superfamily is composed of families and sub-families of enzyme that are defined solely on the basis of their amino acid sequence similarities. With few exceptions, a P450 protein sequence from one fam-ily exhibits upto 40% resemblance to a P450 from other family. P450s with in a single subfamily always share greater than 55% sequence similarity 6,7 .

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