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 by coadministration of mephenytoin and debrisoquin or dextromethorphan. Among the 210 volunteers 21 (10%) were poor metabolizers of debrisoquin/dextromethorphan and two (0.95%) were poor metabolizers of S-mephenytoin. By pooling these data with an earlier study on 156 Estonians, the prevalences of poor metabolizers of debrisoquin/dextromethorphan and poor metabolizers of S-mephenytoin were 7.6% and 2.2%, respectively. The CYP2D6 genotype of 151 subjects was analysed by allele-specific PCR amplification for the defect alleles CYP2D6A and CYP2D6B. All poor metabolizers of debrisoquin carried two defect CYP2D6-alleles. The phenotype (extensive or poor metabolizer) was in all subjects correctly predicted by the genotype. The frequencies of the defect alleles CYP2D6B and CYP2D6A among these 151 subjects (including 14 poor metabolizers-9.3%) were 21.5% and 2.3%, respectively. DNA from 6 subjects with very high CYP2D6 activity (debrisoquin MR < 0.1) was analysed by EcoRI RFLP to identify duplicated or amplified CYP2D6-genes. Two of the subjects were found to carry a duplicated CYP2D6L-gene. In conclusion, the distribution of genetically determined metabolic capacities of CYP2D6 and CYP2C19 in Estonian unrelated subjects did not differ significantly from that in other Caucasian populations. The CYP2D6 phenotype was predicted by PCR-based amplification for the CYP2D6A and CYP2D6B-alleles.
Marandi
T
T
Department of Pharmacology, University of Tartu, Estonia.
Dahl
M L
ML
Kiivet
R A
RA
Rägo
L
L
Sjöqvist
F
F
D000293:Adolescent; D000328:Adult; D000927:Anticonvulsants / Q000378:metabolism / Q000494:pharmacology; D001189:Aryl Hydrocarbon Hydroxylases; D065731:Cytochrome P-450 CYP2C19; D019389:Cytochrome P-450 CYP2D6 / Q000235:genetics*; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics; D003647:Debrisoquin / Q000378:metabolism*; D004957:Estonia; D005260:Female; D005838:Genotype; D006801:Humans; D006900:Hydroxylation; D008297:Male; D008617:Mephenytoin / Q000378:metabolism*; D008875:Middle Aged; D006899:Mixed Function Oxygenases / Q000235:genetics; D010641:Phenotype; D011110:Polymorphism, Genetic / Q000235:genetics; D013565:Sympatholytics / Q000378:metabolism / Q000494:pharmacology
D000927:Anticonvulsants; D013565:Sympatholytics; D003577:Cytochrome P-450 Enzyme System; D006899:Mixed Function Oxygenases; D001189:Aryl Hydrocarbon Hydroxylases; C045793:CYP2C19 protein, human; D065731:Cytochrome P-450 CYP2C19; D019389:Cytochrome P-450 CYP2D6; D008617:Mephenytoin; D003647:Debrisoquin