GENOTYPING OF POLYMORPHIC N-ACETYLTRANSFERASE AND CYP2C19 AND CORRELATION WITH PHARMACOKINETICS AND THERAPEUTIC EFFICACY

Abstract

N-acetyltransferase 2 (NAT2) and cytochrome P450 2C19 enzymes are known to exhibit a hereditarily determined polymorphism. The characterization of genetic variation at the DNA level for these enzymes has made it possible to determine an individual genotype. The common method is a polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP) method using blood samples. We have developed a novel method for determining the NAT2 and CYP2CI9 genotypes using genomic DNA extracted from single hairs, buccal cells and fmgernail. The N-acetylation activity for procainamide and isoniazid was well correlated with NAT2 genotypes. Furthermore, we have first found that the anti-H. pylori efficacy of omeprazole can be related to the CYP2C19 genotype, that is, the eradication effect of omeprazole with amoxicillin was highly efficient in CYP2C19 poor metabolizers, suggesting that CAM or metronidazole needs not to be used for this group on the first line therapy. Genotyping by PCR-RFLP, which is a simple in vitro test, can provide a new strategy to choose an optimal regimen based upon the individual genotype.