• Corpus ID: 40833793

Identification of a new genetic defect responsible for the polymorphism of (S)-mephenytoin metabolism in Japanese.

  title={Identification of a new genetic defect responsible for the polymorphism of (S)-mephenytoin metabolism in Japanese.},
  author={Sonia M F de Morais and Grant R. Wilkinson and Joyce A. Blaisdell and Urs A. Meyer and K. Nakamura and Joyce A. Goldstein},
  journal={Molecular pharmacology},
  volume={46 4},
A genetic polymorphism in the metabolism of the anticonvulsant drug (S)-mephenytoin has been well documented in humans. There are marked interracial differences in the frequency of the poor metabolizer phenotype, which comprises 2-5% of Caucasian but 18-23% of Asian populations. We have recently reported that the principal genetic defect responsible for the poor metabolizer phenotype is a single-base pair mutation in exon 5 of CYP2C19 (CYP2C19m), which accounts for approximately 75-83% of the… 

A new genetic defect in human CYP2C19: mutation of the initiation codon is responsible for poor metabolism of S-mephenytoin.

A new allele is identified in Caucasian PMs which contains an A-->G mutation in the initiation codon which indicates that CYP2C19*4 represents a new PM allele.

Identification of new human CYP2C19 alleles (CYP2C19*6 and CYP2C19*2B) in a Caucasian poor metabolizer of mephenytoin.

Recombinant CYP2C19 6 had negligible catalytic activity toward S-mephenytoin compared with CYP 2C19 1B, which is consistent with the conclusion that CYP1C19*6 represents a PM allele.

Novel mutations in the cytochrome P450 2C19 gene: a pitfall of the PCR-RFLP method for identifying a common mutation

It is reported that two novel mutations in the CYP2C19 gene identified by direct sequencing and subcloning procedures suggest that mutations classed as CYP1C19*3 might include other mutations, and further studies are needed to clarify the relationship between these novel mutations and enzyme activity.

Identification of New Human CYP 2 C 19 Alleles ( CYP 2 C 19 * 6 and CYP 2 C 19 * 2 B ) in a Caucasian Poor Metabolizer of Mephenytoin 1

Two new mutations in CYP2C19 are identified in a single Swiss Caucasian PM outlier whose apparent genotype did not agree with his PM phenotype and these mutations contribute to the PM phenotype in Caucasians.

Frequencies of defective CYP2C19 alleles in a Hong Kong Chinese population: detection of the rare allele CYP2C19*4.

A genetic polymorphism in the metabolism of the anticonvulsant drug mephenytoin in humans is a prime example of interracial and individual variability in drug metabolism. This polymorphism affects

Identification of a null allele of CYP2C9 in an African-American exhibiting toxicity to phenytoin.

The present study reports the first example of a null polymorphism in CYP2C9, which dramatically affects the half-life and clinical toxicity of phenytoin, and demonstrates the severe clinical consequences to patients with a null mutation after treatment with normal doses of phenYtoin.

Identification and functional characterization of new potentially defective alleles of human CYP2C19.

Three new potentially defective alleles of CYP2C19 occur in African-Americans, or individuals of African descent, and are predicted to alter risk of these populations to clinically important drugs.

Genetic Polymorphism of Cytochrome P450 2C19

The measurement of S-mephenytoin hydroxylation led to discover that CYP2C19 polymorphism in human is mediated through an autosomal recessive trait, which would lead to increasing risk of either therapeutic failures or misadventures.

A novel transversion in the intron 5 donor splice junction of CYP2C19 and a sequence polymorphism in exon 3 contribute to the poor metabolizer phenotype for the anticonvulsant drug S-mephenytoin.

Two new allelic variants that contribute to the PM phenotype in Caucasians are isolated and Restriction fragment length polymerase chain reaction tests were developed to identify the new allele variants.

Identification of New CYP2C19 Variants Exhibiting Decreased Enzyme Activity in the Metabolism of S-Mephenytoin and Omeprazole

Characterizes the allele frequency and haplotype distribution of CYP2C19 in a Korean population and provides functional analysis of new coding variants of the CYP 2C19 gene, suggesting that individuals carrying CYP3C19*26 would have lower activity for metabolizing CYP1C19 substrate drugs.