Analysis of CYP3A4*1B and CYP3A5*3 polymorphisms in population of Bosnia and Herzegovina.
OBJECTIVE
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, CYP3A4*1B and CYP3A5*3, 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 CYP3A5*3, while CYP3A4*1B was genotyped by high-resolution melting analysis.


RESULTS
Our results have shown that the distribution of CYP3A4*1B and CYP3A5*3 alleles was in line with the data reported in European Caucasians. We confirmed that CYP3A4*1B mutant allele is rare in Caucasians, being present in only 5.1% individuals. However, CYP3A5*3 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 CYP3A5*3 and CYP3A4*1B alleles. No significant difference in allele frequencies for CYP3A4*1B and CYP3A5*3 has been shown between male and female subjects participating in our study.


CONCLUSIONS
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.
Department for Biochemistry and Clinical Analysis, Faculty of Pharmacy, University of Sarajevo, Sarajevo, Bosnia and Herzegovina. sabinasemiz@hotmail.com
Sabina
S
Semiz
Tanja
T
Dujić
Barbara
B
Ostanek
Besim
B
Prnjavorac
Tamer
T
Bego
Maja
M
Malenica
Barbara
B
Mlinar
Janja
J
Marc
Adlija
A
Causević
D017522:Bosnia and Herzegovina; D051544:Cytochrome P-450 CYP3A / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D005828:Genetics, Population; D005838:Genotype; D006801:Humans; D008297:Male; D011110:Polymorphism, Genetic
C510164:CYP3A5 protein, human; D051544:Cytochrome P-450 CYP3A; C510163:CYP3A4 protein, human