Genetic polymorphisms of cytochromes P450: CYP2C9, CYP2C19, and CYP2D6 in Croatian population.

Aim: To determine the prevalence of most common mutations of cytochrome P450 (CYP), ie, allelic variants of CYP2C9, CYP2C19, and CYP2D6, and to predict genotype frequency in the Croatian population.

Methods: CYP genotype was determined in 200 non-related Croatian citizens. DNA isolated from blood samples was used for the analysis of the most common allelic variants of CYP2C9, CYP2C19, and CYP2D6 by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method.

Results: For 200 subjects genotyped for CYP2C9, the allele frequencies of CYP2C9*1 (wt), CYP2C9*2, and CYP2C9*3 were 0.74, 0.165, and 0.095, respectively. Among them, 3.5% of subjects were predicted to be poor metabolizers. For CYP2C19, the most frequent alleles were CYP2C19*1 and CYP2C19*2, with frequencies of 0.85 and 0.15, respectively; 3% of subjects were predicted to be poor metabolizers. For CYP2D6, the most frequent alleles were CYP2D6*1 (frequency 0.765), CYP2D62* (0.04), CYP2D6*3 (0.0275), CYP2D6*4 (0.14), CYP2D6*5 ( 0.01), and CYP2D6*6 (0.015). Out of these, 3% were predicted to be poor metabolizers, and 4% were predicted to be ultra-rapid metabolizers.

Conclusion: The prevalence of allelic variants and predicted genotypes in the Croatian population is in accordance with the other European populations, and it can be interpolated between the values for mid-European and Mediterranean populations.