Molecular basis of polymorphic drug metabolism

Genetic polymorphisms with functional effects occur in many of the genes encoding drug metabolizing enzymes and are an important cause of adverse drug reaction. Recent advances in the understanding of the molecular genetics of drug-metabolizing enzymes, particularly the cytochromes P450, has enabled...

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Bibliographic Details
Published inJournal of molecular medicine (Berlin, Germany) Vol. 73; no. 11; p. 539
Main Author Daly, A K
Format Journal Article
LanguageEnglish
Published Germany 01.11.1995
Subjects
Alleles
Cytochrome P-450 Enzyme System - genetics
Cytochrome P-450 Enzyme System - metabolism
Humans
Hydrolases - genetics
Hydrolases - metabolism
Oxidation-Reduction
Oxidoreductases - genetics
Oxidoreductases - metabolism
Pharmaceutical Preparations - metabolism
Polymorphism, Genetic
Transferases - genetics
Transferases - metabolism
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Summary:Genetic polymorphisms with functional effects occur in many of the genes encoding drug metabolizing enzymes and are an important cause of adverse drug reaction. Recent advances in the understanding of the molecular genetics of drug-metabolizing enzymes, particularly the cytochromes P450, has enabled the molecular basis of several polymorphisms to be elucidated and genotyping assays using the polymerase chain reaction to be developed. Polymorphisms in this category include those in the cytochrome P450 genes CYP2D6, CYP2C19, CYP2A6, CYP2C9 and CYP2E1, the glutathione S-transferase genes GSTM1 and GSTT1 and the N-acetyltransferase gene NAT2. The molecular basis and importance to drug metabolism of the various polymorphisms as well as evidence for the existence of polymorphisms in other genes encoding drug-metabolizing enzymes such as the UDP-glucuronosyltransferases, the sulphotransferases and the methyltransferases are discussed.
ISSN:0946-2716
DOI:10.1007/bf00195139