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


CONCLUSIONS
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.
Bozina
Nada
N
University Institute of Laboratory Diagnosis, Zagreb University Hospital Center and School of Medicine, Zagreb, Croatia. cbi-zg@zg.tel.hr
Granić
Paula
P
Lalić
Zdenka
Z
Tramisak
Inja
I
Lovrić
Mila
M
Stavljenić-Rukavina
Ana
A
D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics*; D016009:Chi-Square Distribution; D016001:Confidence Intervals; D017523:Croatia; D065731:Cytochrome P-450 CYP2C19; D065729:Cytochrome P-450 CYP2C9; D019389:Cytochrome P-450 CYP2D6 / Q000235:genetics*; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D005828:Genetics, Population; D006801:Humans; D008297:Male; D006899:Mixed Function Oxygenases / Q000235:genetics*; D009154:Mutation; D011110:Polymorphism, Genetic; D011159:Population Surveillance; D011336:Probability; D012680:Sensitivity and Specificity
D003577:Cytochrome P-450 Enzyme System; D006899:Mixed Function Oxygenases; C450260:CYP2C9 protein, human; D065729:Cytochrome P-450 CYP2C9; D001189:Aryl Hydrocarbon Hydroxylases; C045793:CYP2C19 protein, human; D065731:Cytochrome P-450 CYP2C19; D019389:Cytochrome P-450 CYP2D6