Prediction of phenotype for acetylation and for debrisoquine hydroxylation by DNA-tests in healthy human volunteers.
The debrisoquine/sparteine-type polymorphism of drug oxidation and the polymorphism for acetylation are two common inherited variations in human drug metabolism. The phenotypes for hydroxylation and acetylation can be predicted be newly developed methods based on mutation-specific amplification of DNA by the polymerase chain reaction (PCR), which also allow for identification of heterozygous carriers of one mutant allele. In the present study, the results of genotyping of 81 healthy European volunteers were compared with the phenotype obtained by the classical biochemical approach using debrisoquine and caffeine as probe drugs. Genotyping correctly predicted all 73 extensive metabolisers (EMs) and 6 out of 8 poor metabolisers (PMs) of debrisoquine. All 48 rapid acetylators and 33 of 35 slow acetylators were predicted. Overall, the DNA analysis result matched the in vivo phenotype in 97.5% of individuals.
Graf
T
T
Department of Research and Development, Ciba-Geigy Ltd., Basel, Switzerland.
Broly
F
F
Hoffmann
F
F
Probst
M
M
Meyer
U A
UA
Howald
H
H
D000107:Acetylation; D000328:Adult; D003647:Debrisoquin / Q000378:metabolism*; D005260:Female; D005784:Gene Amplification; D005838:Genotype; D006801:Humans; D006900:Hydroxylation; D008297:Male; D008875:Middle Aged; D009154:Mutation; D010641:Phenotype; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic / Q000235:genetics*; D013034:Sparteine / Q000378:metabolism*
D013034:Sparteine; D003647:Debrisoquin