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

J Hum Genet. 2006;51(2):118-123. doi: 10.1007/s10038-005-0332-y. Epub 2005 Nov 24.

Abstract

CYP2C19 is a clinically important enzyme involved in the metabolism of therapeutic drugs such as (S)-mephenytoin, omeprazole, proguanil, and diazepam. Individuals can be characterized as either extensive metabolizers (EM) or poor metabolizers (PM) on the basis of CYP2C19 enzyme activity. The PM phenotype occurs in 2-5% of Caucasian populations, but at higher frequencies (18-23%) in Asians. CYP2C19*2 and CYP2C19*3, which are single-nucleotide polymorphisms of CYP2C19, are the main cause of PM phenotyping in homozygotes or compound heterozygotes. We report two novel mutations in the CYP2C19 gene identified by direct sequencing and subcloning procedures. One of these mutations was considered to be CYP2C19*3 by polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP). This result suggests that mutations classed as CYP2C19*3 might include other mutations. Further studies are needed to clarify the relationship between these novel mutations and enzyme activity.

Publication types

  • Comparative Study

MeSH terms

  • Adult
  • Alleles*
  • Aryl Hydrocarbon Hydroxylases / classification
  • Aryl Hydrocarbon Hydroxylases / genetics*
  • Aryl Hydrocarbon Hydroxylases / metabolism
  • Base Sequence
  • Cloning, Molecular
  • Cytochrome P-450 CYP2C19
  • DNA Primers
  • Genetic Carrier Screening
  • Humans
  • Mixed Function Oxygenases / classification
  • Mixed Function Oxygenases / genetics*
  • Mixed Function Oxygenases / metabolism
  • Molecular Sequence Data
  • Mutation / genetics*
  • Polymorphism, Restriction Fragment Length*
  • Restriction Mapping / methods*
  • Sequence Analysis, DNA

Substances

  • DNA Primers
  • Mixed Function Oxygenases
  • Aryl Hydrocarbon Hydroxylases
  • CYP2C19 protein, human
  • Cytochrome P-450 CYP2C19