engleski

Genetic polymorphism of Cytochrome P450 CYP2D6 and CYP2C9 enzymes among Croatian population

Greatest part of xenobiotic metabolism includes oxidative reactions on enzyme system Cytochrome P450. Persons with two defective alleles poorly metabolize particular drugs (Poor Metabolizer phenotype – PM), those with only one disrupted gene are Intermediate metabolizers (IM), and those with both completely functional alleles are Extensive metabolizers (EM). CYP2D6 is one of the most important polymorphic cytochrome P-450 and metabolizes more than 30 commonly prescribed drugs. Wild type allele is CYP2D6*1, and most abundant null alleles are CYP2D6*3, *4, *6, *7, and *8. Another important enzyme is CYP2C9. Polymorphic null alleles are CYP2C9*2 and CYP2C9*3. The genetic polymorphism of those enzymes has an important role in adverse therapeutic effects or even in the prevalence of cancer or other diseases. Our study aim was to assess the CYP2D6 and CYP2C9 allelic prevalence, genotypes and predicted phenotypes among Croatian population. We genotyped 145 healthy subjects on CYP2D6 (mean age 31, SD = 11, 31% women) and 142 subjects on CYP2C9 (mean age 38, SD = 11, 30% women). Between-sex frequencies were concordant to Hardy – Weinberg equilibrium (pCHI>0.05). CYP2D6 genotyping was performed by multiplex allele specific PCR method (Štefanović M. et al., 2001) and CYP2C9 genotyping by PCR-RFLP (method by Yasar U. et al., 1999). Allelic frequencies for CYP2D6 were as follows: *3 – 1.4%, - *4 – 11.0%, *6 – 1.0% and *1(wt) – 86.6%. CYP2C9 allelic frequencies were *2 – 21.9%, *3 – 5.3% and *1 – 72.8%. Genotype frequencies for the CYP2D6 were *3/wt – 2.8%, *4/wt – 18.6%, *4/*4 – 1.4%, *6/wt – 1.4%, *4/*6 – 0.7% and wt/wt - 75.2%. CYP2C9 genotype frequencies were wt/wt – 69.0%, wt/*2 – 26.1%, *3/wt – 3.5%, *2/*3 -0.7%, and *2/*2 – 0.7%. Predicted phenotype frequencies for CYP2D6 were IM – 22.8% and PM – 2.8%. For CYP2C9 we found IM – 29.6 and PM – 1.4%. Results showed concordance to similar studies among south European Caucasian population. In the future we plan to continue our work to genotype more representative number of the population.

CYP450; xenobiotic metabolism; CYP2D6; CYP2C9

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