Cytochrome P450 polymorphism--molecular, metabolic, and pharmacogenetic aspects. III. Influence of CYP genetic polymorphism on population differentiation of drug metabolism phenotype.
In the human genome 684 alleles of CYP genes, and additionally 30 complete CYP pseudogenes, have been identified. So far 388 isoforms of 58 human CYP isoenzymes have been described at the phenotypic level. The molecular forms of many CYP isoenzymes responsible for drug biotransformation show a differentiated degree of specific catalytic activity - from increased, through normal and decreased to various extent, to trace or even absent. Depending on the homo- or heterozygous genotype, a broad palette of phenotypic forms may be present, differentiated in respect to biotransformation dynamics of specific drugs. The progress of molecular biology with particular consideration of genotyping and DNA microarray technologies has created a basis for the dynamic progress of pharmacogenetics, allowing fast and sensitive determination of the individual pharmacogenetic profile, encompassing a large set of CYP alleles extended by allelic variants of genes encoding other enzymes participating in drug metabolism. The possibility to evaluate the pharmacogenetic profile of patients together with the increasing knowledge about the mechanisms of inhibition, repression and also induction of enzymes participating in biotransformation of xenobiotics and endogenous compounds create increasing possibilities of elaborating optimal individualized pharmacotherapeutic strategies.
Tomaszewski
Piotr
P
Department of Biochemistry and Clinical Chemistry, Pharmaceutical Faculty, Medical University of Warsaw, Warsaw, Poland. piotrtomaszewski@poczta.onet.pl
Kubiak-Tomaszewska
Grazyna
G
Łukaszkiewicz
Jacek
J
Pachecka
Jan
J
D000483:Alleles; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007527:Isoenzymes / Q000235:genetics / Q000378:metabolism; D004364:Pharmaceutical Preparations / Q000378:metabolism*; D010597:Pharmacogenetics; D010641:Phenotype; D011110:Polymorphism, Genetic
D007527:Isoenzymes; D004364:Pharmaceutical Preparations; D003577:Cytochrome P-450 Enzyme System