Prevalence of five pharmacologically most important CYP2C9 and CYP2C19 allelic variants in the population from the Republic of Srpska in Bosnia and Herzegovina.

Stojko Vidović,Svjetlana Stoisavljević-Šatara,Jelena Bećarević,Vanja Vidović,Miloš P. Stojiljković,Ranko Škrbić,Nela Maksimović

doi:10.2478/aiht-2021-72-3499

Stojko Vidović, Svjetlana Stoisavljević-Šatara + Show 5 more

Open Access

https://doi.org/10.2478/aiht-2021-72-3499

Copy DOI

Abstract

The enzymes of the cytochrome P450 superfamily play a critical role in phase I drug metabolism. Among them, CYP2C9 and CYP2C19 are clinically important, as they can mediate severe toxicity, therapy failure, and increased susceptibility to cancer and other diseases caused by chemicals. The aim of this study was to determine the prevalence of pharmacologically most important allelic variants of the CYP2C9 and CYP2C19 genes in the general population of the Republic of Srpska (Bosnia and Herzegovina) and to compare them with other populations. For this purpose we determined the genotype profile and allele frequency of 216 randomly selected healthy volunteers using real-time polymerase chain reaction (RT-PCR). The prevalence of the CYP2C9 *2 and *3 alleles was 13.6 and 7.4 %, respectively. Based on these frequencies, of the 216 participants four (1.86 %) were predicted to be poor metabolisers, 78 (36.11 %) intermediate, and the remaining 134 (62.03 %) normal metabolisers. Based on the prevalence of CYP2C19 *2 and *17 variants – 16.2 and 20.4 %, respectively – nine (4.17 %) were predicted to be poor, 57 (26.39 %) rapid, and nine (4.17 %) ultra-rapid metabolisers. We found no significant differences in allele frequencies in our population and populations from other European countries. These findings suggest that genetically determined phenotypes of CYP2C9 and CYP2C19 should be taken into consideration to minimise individual risk and improve benefits of drug therapy in the Republic of Srpska.

Highlights

The enzymes of the cytochrome P450 superfamily play a critical role in phase I drug metabolism
The cytochrome P450 (CYP) superfamily consists of enzymes with highly diverse roles in the metabolism of drugs, fatty acids, steroids, and xenobiotics [1, 2]. Their genetic variants, single nucleotide polymorphisms (SNPs) in particular, can lead to therapy failure, severe toxicity, and increased susceptibility to cancer and other diseases caused by chemicals [3]
CYPs make about 80 % of all drug metabolising enzymes (DMEs), most notably those participating in phase I metabolism, such as flavincontaining monooxygenases, epoxide hydrolases, and many other oxidising, reducing, and hydrolysing enzymes [4]

Summary

Introduction

The enzymes of the cytochrome P450 superfamily play a critical role in phase I drug metabolism. The cytochrome P450 (CYP) superfamily consists of enzymes with highly diverse roles in the metabolism of drugs, fatty acids, steroids, and xenobiotics [1, 2] Their genetic variants, single nucleotide polymorphisms (SNPs) in particular, can lead to therapy failure, severe toxicity, and increased susceptibility to cancer and other diseases caused by chemicals [3]. Bearing in mind various types of mutation caused by SNPs, genotyping the most relevant CYP enzymes could identify patients at risk of developing adverse drug reactions and increase treatment safety and efficiency [3] In this respect, CYP enzymes CYP2C9 and CYP2C19 are among clinically most relevant, as they metabolise about 20–30 %. Allelic variant *3 is very rare in Europeans and Africans (1 %) but not as rare in Asians (8 %) [15, 17]

Objectives

Methods

Conclusion