Analysis of CYP3A4*1B and CYP3A5*3 polymorphisms in population of Bosnia and Herzegovina.

AIM

Differences in the frequency of distribution of the cytochrome P450 (CYP) allelic variants have been demonstrated between distinct ethnic groups, contributing to observed interindividual variation in drug response. In this study we determined, for the first time, prevalence of the common allelic variants of the polymorphic CYP enzymes, CYP3A41B and CYP3A53, in the population of Bosnia and Herzegovina (BH).

METHODS

Genomic DNA was extracted from blood samples collected from 140 unrelated subjects. A real-time PCR was used for the detection of CYP polymorphisms, with the application of the specific TaqMan SNP Genotyping Assay (Applied Biosystems) for CYP3A53, while CYP3A41B was genotyped by high-resolution melting analysis.

RESULTS

Our results have shown that the distribution of CYP3A41B and CYP3A53 alleles was in line with the data reported in European Caucasians. We confirmed that CYP3A41B mutant allele is rare in Caucasians, being present in only 5.1% individuals. However, CYP3A53 polymorphism was found to be predominant in the Bosnian population with an incidence of 94%, similarly to other European populations tested so far. Interestingly, we have demonstrated a strong linkage disequilibrium between CYP3A53 and CYP3A41B alleles. No significant difference in allele frequencies for CYP3A41B and CYP3A53 has been shown between male and female subjects participating in our study.

CONCLUSION

Our data demonstrated the high prevalence of CYP3A5*3 allele in Bosnian population, indicating significance of analysis of CYP3A5 and CYP3A4 polymorphisms and corresponding allele frequencies in specific ethnic groups. Importantly, results of this study may lead to translation of pharmacogenetics and individualized therapeutic approach in current clinical practices in BH.