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

Semiz, Sabina (author), Dujić, Tanja (author), Ostanek, Barbara (author), Prnjavorac, Besim (author), Bego, T. (author), Malenica, M. (author), Mlinar, Barbara (author), Marc, Janja (author), Čaušević, A. (author)

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 irst 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 speciic TaqManr 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 conirmed 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 signiicant difference in allele frequencies for CYP3A4*1B and CYP3A5*3 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 signiicance of analysis of CYP3A5 and CYP3A4 polymorphisms and corresponding allele frequencies in speciic ethnic groups. Importantly, results of this study may lead to translation of pharmacogenetics and individualized therapeutic approach in current clinical practices in BH.

• Language: English
• Keywords: citokrom P450, CYP3A4, CYP3A5, farmakogenetika
• Work type: Not categorized (r6)
• Tipology: 1.01 - Original Scientific Article
• Organization: FFA - Faculty of Pharmacy
• Year: 2011
• Number of pages: str. 84-89
• Numbering: Vol. 8, no. 1
• UDC: 577.2
• ISSN on article: 1840-0132
• COBISS.SI-ID: 2957425
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Record is a part of a journal

• Title: Medicinski glasnik
• Shortened title: Med. glas. Ljek. komore Zeničko-doboj. kantona
• Publisher: Ljekarska komora Ze-Do kantona
• ISSN: 1840-0132
• COBISS.SI-ID: 3030904

Secondary language

• Language: English

Abstract

Cilj Postojanje značajnih razlika u frekvenciji različitih alelskih varijanti citohroma P450 (CYP) među različitim etničkim grupama doprinosi interindividualnoj razlici odgovora na terapiju lijekovima. Ovo je prva studija u kojoj smo analizirali prevalencu alelskih varijanti polimorfnih CYP enzima, CYP3A4*1B i CYP3A5*3, u populaciji iz Bosne i Hercegovine (BiH). Metode Genomska DNK izolovana je iz uzoraka krvi, uzetih od 140 nesrodnih osoba. U cilju detekcije navedenih CYP polimorizama korištena je metoda RT-PCR, uz aplikaciju speciičnih TaqManr SNP testova (Applied Biosystems) za CYP3A5*3, dok je CYP3A4*1B genotipiziran uz korištenje analize taljenja DNK visoke rezolucije. Rezultati Rezultati ove studije pokazali su da je distribucija CYP3A4*1B i CYP3A5*3 alela u skladu s podacima ranije objavljenim za evropsku populaciju bjelaca. Potvrdili smo da je CYP3A4*1B mutant alela rijetka kod bjelaca i prisutna kod samo 5.1% individua. Međutim, naši su rezultati pokazali da je CYP3A5*3 polimorizam dominantan kod bosanskohercegovačke populacije, s incidencom od 94%, što je slično nalazima u drugim testiranim evropskim populacionim grupama. Interesantno je da smo zabilježili značajnu neravnotežu veze (linkage disequilibrium) između CYP3A5*3i CYP3A4*1B alela. Nije primjećena signiikantna razlika u frekvenciji CYP3A4*1B i CYP3A5*3 alela između osoba muškog i ženskog spola koje su učestvovale u našoj studiji. Zaključak Naši rezultati pokazali su visoku prevalencu CYP3A5*3 alele u bosanskohercegovačkoj populaciji, demonstrirajući značaj analize CYP3A4 i CYP3A5 polimorizama i frekvencije odgovarajućih alela kod speciičnih etničkih grupa. Važno je istaći da rezultati ove i sličnih budućih studija, mogu dovesti do bržeg uvođenja farmakogenetike i individualiziranog terapeutskog pristupa u sadašnju kliničku praksu u BiH.