Frequencies of Defective CYP2C19 Alleles in a Hong Kong Chinese Population: Detection of the Rare Allele CYP2C19*4

Abstract

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 the metabolism of several other clinically used drugs, some of which are of interest in psychopharmacotherapy (1). The polymorphic enzyme that 4′-hydroxylates S -mephenytoin is known as CYP2C19 (2). In subjects deficient for CYP2C19, drugs metabolized by this enzyme may be associated with toxic concentrations or therapeutic failure when administered in dosages within the normal dosage range. Depending on the activity of CYP2C19, individuals can be characterized phenotypically as extensive metabolizers or poor metabolizers (PMs) of S -mephenytoin. CYP2C19 is encoded by the CYP2C19 gene, and its defective alleles account for the PM phenotype, which is inherited as an autosomal recessive trait (3). There is a marked interethnic difference in the distribution of this polymorphism, with the PM phenotype found in 2–5% of Caucasians but in 13–23% of Orientals (4)(5). The main defective allele, CYP2C192 , accounts for ∼75–85% of alleles responsible for the PM phenotype in both Orientals and Caucasians (4). CYP2C193 is extremely rare in …