Genetic polymorphism of cytochrome P450 and methods for its determination.
The majority of human P450 dependent drug metabolism is carried out by polymorphic enzymes which can alter plasma concentration of the pharmacological active substance followed by an enhanced or suppressed pharmacological effect. The response of individual patients to drugs can be affected by variations in DNA sequence mainly by single nucleotide polymorphisms (SNPs). Knowledge of functionally important SNPs prior to the drug administrations may assist in the development of individualized pharmacotherapy avoiding unexpected drug responses, such as harmful adverse drug reactions or treatment failures. This review discusses both the basic characteristics of the major polymorphic cytochrome P450 enzymes and examines the pharmacogenetic methods employed to estimate metabolic status. We will focus mainly on the basic principles of genotyping assays involving molecular biology tools.
Buzková
H
H
Clinical Pharmacology Unit of the Department of Pharmacology of the First Faculty of Medicine, Charles University in Prague, Czech Republic. hbuzk@lf1.cuni.cz
Pechandová
K
K
Slanar
O
O
Perlík
F
F
D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics; D065731:Cytochrome P-450 CYP2C19; D019389:Cytochrome P-450 CYP2D6 / Q000235:genetics; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics*; D005838:Genotype; D006801:Humans; D006899:Mixed Function Oxygenases / Q000235:genetics; D010641:Phenotype; D011110:Polymorphism, Genetic; D020641:Polymorphism, Single Nucleotide; D018807:Polymorphism, Single-Stranded Conformational
D003577:Cytochrome P-450 Enzyme System; D006899:Mixed Function Oxygenases; D001189:Aryl Hydrocarbon Hydroxylases; C045793:CYP2C19 protein, human; D065731:Cytochrome P-450 CYP2C19; D019389:Cytochrome P-450 CYP2D6