[Genotyping of CYP2D6 and CYP2C19].
BACKGROUND
Polymorphisms in drug metabolizing enzymes are considered as a major factor influencing the incidence of adverse drug reactions or failure of pharmacotherapy. Our aim was to compare the distribution of functional polymorphisms in the genes CYP2D6 and CYP2C19 between healthy control group and of patients reffered to our department due to adverse drug reactions or insufficient efficacy of a treatment.


RESULTS
The group of patients comprised of 60 subjects, 218 healthy unrelated subjects were included in the cotrol group. In both groups genotypes of CYP2D6 and CYP2C19 were analyzed. There were significantly fewer extensive metabolizers of CYP2D6 in the patient group comparison with healthy control subjects (25.0% vs. 49.8%) while the proportion of intermediate metabolizers was significantly higher than in helthy population (58.3% vs. 38.5%). We also observed more poor metabolizers than in control group (13.3% vs. 6.8%), but the difference did not reach level of statistical significance probably due to low number of subjects. The distribution of either ultrarapid metabolizers of CYP2D6 or deficient alleles of CYP2C19 was similar in both groups.


CONCLUSIONS
Clinically apparent alteration of drug effects are often caused by partial or complete deficit of CYP2D6 activity. Our results confirm the importance of CYP2D6 polymorphisms on the efficycy and safety of pharmacotherapy.
Slanar
O
O
Ustav klinické biochemie a laboratorní diagnostiky 1. LF UK a VFN, Praha 2 0dd4lenf klinicke farmakologie 1. LF UK a VFN, Praha. oslan@lf1.cuni.cz
Drazd'áková
M
M
Babiárová
K
K
Pechandová
K
K
Buzková
H
H
Perlík
F
F
Zima
T
T
D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics*; D065731:Cytochrome P-450 CYP2C19; D019389:Cytochrome P-450 CYP2D6 / Q000235:genetics*; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D006899:Mixed Function Oxygenases / Q000235:genetics*; D010597:Pharmacogenetics; D010599:Pharmacokinetics; D011110:Polymorphism, Genetic
D006899:Mixed Function Oxygenases; D001189:Aryl Hydrocarbon Hydroxylases; C045793:CYP2C19 protein, human; D065731:Cytochrome P-450 CYP2C19; D019389:Cytochrome P-450 CYP2D6