engleski

Polymorphism of CYP2C9 and CYP2D6 in Predicting Drug Metabolism Phenotype

CYP2C9 and CYP2D6 are highly polymorphic enzymes metabolizing anticoagulant and antipsychotic drugs, respectively. Two CYP2C9 alleles, 2C9*2 and 2C9*3, encode for enzymes with 16%– ; ; 20% and 5% of normal activity, respectively. Six CYP2D6 alleles (*3, *4, *5, *6, *7 and *8) encode for inactive enzymes. The aim was to study frequency of 2C9 and 2D6 alleles in healthy Croatian population and assess the association between CYP2D6 polymorphism and side effect in psychiatric patients (n=87) on therapy more than 3 years. The CYP2C9 alleles were identified by PCR-RFLP and CYP2D6 alleles by multiplex PCR. In controls, the frequency of CYP2C9 *2 and *3 allele was 12.7% and 2.9%, respectively, somewhat lower than in Caucasians. Genotype distribution showed 27.5% as heterozygous with one, and 2.0% as heterozygous with two mutations. The results on 2D6 indicated a significant allele (p=0.015, odds=2.542), genotype (p=0.016) and phenotype (p=0.025, odds=5.020) difference between controls and psychiatric patients. Considerably higher frequency of heterozygous (34.2%) and homozygous (13.2%) 2D6*4 allele was found in patients with (n=39) and without (n=48) side effect. The odds ratio of 2.626 for 2D6*4 and of 5.333 for 2D6*6 alleles suggested their significant association with side effect in patients on long-term therapy.

CYP2C9 ; CYP2D6 ; anticoagulant and antipsychotic drugs ; side effect

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