Genotyping of CYP2D6 and CYP2C19
1,2Slanař O., 1Dražďáková M., 1Babiárová K., 2Pechandová K., 2Buzková H., 2Perlík F., 1Zima T.
1Ústav klinické biochemie a laboratorní diagnostiky 1. LF UK a VFN, Praha 2Oddělení klinické farmakologie 1. LF UK a VFN, Praha |
|
Summary:
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.
Methods and 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.
Key words:
cytochrome P450, polymorphism, adverse drug reactions, pharmacogenetics
|