DEBRISOQUIN AND S-MEPHENYTOIN HYDROXYLATION PHENOTYPES AND CYP2D6 GENOTYPES IN AN ESTONIAN POPULATION

The polymorphisms of debrisoquin (CYP2D6) and S-mephenytoin (CYP2C19) hydroxylation were studied in 210 unrelated healthy native Estonians b y coadministration of mephenytoin and debrisoquin or dextromethorphan. Among the 210 volunteers 21 (10%) were poor metabolizers of debrisoqu in/dextromethorphan and two (0.95%) were poor metabolizers of S-mephen ytoin. By pooling these data with an earlier study on 156 Estonians, t he prevalences of poor metabolizers of debrisoquin/dextromethorphan an d poor metabolizers of S-mephenytoin were 7.6% and 2.2%, respectively. The CYP2D6 genotype of 151 subjects was analysed by allele-specific P CR amplification for the defect alleles CYP2D6A and CYP2D6B. All poor metabolizers of debrisoquin carried two defect CYPZD6-alleles. The phe notype (extensive or poor metabolizer) was in all subjects correctly p redicted by the genotype. The frequencies of the defect alleles CYP2D6 B and CYP2D6A among these 151 subjects (including 14 poor metabolizers - 9.3%) were 21.5% and 2.3%, respectively. DNA from 6 subjects with v ery high CYP2D6 activity (debrisoquin MR<0.1) was analysed by EcoRI RF LP to identify duplicated or amplified CYP2D6-genes. Two of the subjec ts were found to carry a duplicated CYP2D6L-gene. In conclusion, the d istribution of genetically determined metabolic capacities of CYP2D6 a nd CYP2C19 in Estonian unrelated subjects did not differ significantly from that in other Caucasian populations. The CYP2D6 phenotype was pr edicted by PCR-based amplification for the CYP2D6A and CYP2D6B-alleles .