Genetic polymorphism of CYP2D6 in Korean population

Genotyping of CYP2D6 has been addressed only for CYP2D6*10B in the Korean population. However, we found that CYP2D6*10B genotype alone could not explain the disposition of paroxetine, one of CYP2D6 substrates, in Korean subjects (Clin Pharmal & Ther, 2000:67:567-576). We explored another CYP2D6 mutant allele that influences on the CYP2D6 activity in 216 Korean healthy subjects. Genotypes of CYP2D6*5, *10B, *17, *18 were determined by allele specific PCT or PCR-RFLP and CYP2D6*21 genotyping by SSCP and sequencing of PCR product. Results are as in table heterozygous homozygous allele frequency CYP2D6*5 19/216(8.8%) 3/216(1.4%) 5.87% CYP2D6*10B 108/216(50.0%) 52.216(24.1%) 49.0% CYP2D6*17 0 0 0 CYP2D6*18 0 0 0 CYP2D6*21 1/216(0.46%) 0 0.25% One subject who has far greater metoprolol MR(8.97) than any other homozygous subjects for CYP2D6*10B was identified to have heterozygous CYP2D6*21 mutation. CYP2D6*5 seems to be another important CYP2D6 genotype in addition to CYP2D6*10B in Korean subjects. Routine genotyping of CYP2D6*5 and CYP2D6*10B would increase the predictability of CYP2D6 activity in this population.