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The major genetic defect responsible for the polymorphism of S-mephenytoin metabolism in humans.
It is reported that the principal defect in poor metabolizers is a single base pair (G-->A) mutation in exon 5 of CYP2C19, which creates an aberrant splice site that results in a truncated, non-functional protein. Expand
Pharmacogenetics and adverse drug reactions
  • U. Meyer
  • Medicine, Biology
  • The Lancet
  • 11 November 2000
Pharmacogenomic techniques allow efficient analysis of these risk factors, and genotyping tests have the potential to optimise drug therapy in the future. Expand
Human arylamine N-acetyltransferase genes: isolation, chromosomal localization, and functional expression.
Data suggest that NAT2 encodes the polymorphic NAT protein, a target of a common genetic polymorphism of clinical relevance in human populations, as judged by their NAT enzyme activity with the arylamine substrate sulfamethazine. Expand
Induction of drug metabolism: the role of nuclear receptors.
In this review, recent findings regarding xenosensors and their target genes are summarized and are put into an evolutionary perspective in regard to how a living organism has derived a system that is able to deal with potentially toxic compounds it has not encountered before. Expand
Regulation of CYP3A4 by the bile acid receptor FXR: evidence for functional binding sites in the CYP3A4 gene.
It is shown that physiological concentrations of the primary bile acids chenodeoxycholic acid regulate the expression of CYP3A4 via the bile acid receptor FXR, which may explain elevated CYP2A expression in cholestasis and part of the variability of drug responsiveness and toxicity between individuals. Expand
Identification of a new genetic defect responsible for the polymorphism of (S)-mephenytoin metabolism in Japanese.
A new mutation is identified in Japanese poor metabolizers, consisting of a guanine to adenine mutation at position 636 of exon 4 of CYP2C19, which creates a premature stop codon. Expand
Identification and functional characterization of eight CYP3A4 protein variants.
A study of 213 Middle and Western European DNA samples resulted in the identification of 18 new CYP3A4 variants, including eight protein variants that may play a role in the atypical response to drugs or altered sensitivity to carcinogens. Expand
Oxidation of midazolam and triazolam by human liver cytochrome P450IIIA4.
The data provide evidence that the marked interindividual variation in the response to these widely used benzodiazepine drugs is due to variable hepatic metabolism, and predominantly mediated by cytochrome P450IIIA4. Expand
Polymorphism of the cytochrome P450 CYP2D6 gene in a European population: characterization of 48 mutations and 53 alleles, their frequencies and evolution.
These data provide a solid basis for future epidemiological, clinical as well as interethnic studies of the CYP2D6 polymorphism and highlight that the described single strand conformation polymorphism method can be successfully used in designing such studies. Expand
Molecular mechanism of slow acetylation of drugs and carcinogens in humans.
A simple DNA amplification assay is developed that allows the predictive genotyping of more than 95% of slow and rapid acetylator alleles and the identification of individuals at risk. Expand