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

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.

Genetic Polymorphisms of Cyp2c9 Gene Among Voluntary Donors From the Macedonian Bone Marrow Donor Registry and Its Implications on Therapeutic Dosage of Non-Steroidal Anti-Inflammatory Drugs

“…On the other hand, the frequency of CYP2C9*1*3 carriers in this study was much higher compared to earlier published data for Macedonians (10.3%), Serbians (12.04%), Croatians (12.78%), and Greeks (13.43%) [10][11][12][13] . In our study population, we detected only one PMs with CYP2C9*2*3 genotype (4%) as expected from the previously published data for Macedonians (1%) and Serbians (0.93%) [10,11] . According to the published data, PMs are more prevalent in Croatians and Greeks where they account for 1.94% and 1.41% of all types of metabolizers, respectively [12,13] .…”

“…The frequency of IMs we obtained was much higher in Macedonians than in Serbians (36.11%). As for CYP2C9*1*2 carriers in our study, the percentage was slightly decreased compared to previously published data for Macedonians (19.6%), Serbians (21.76%), Croatians (23.52%), and Greeks (20.14%) [10][11][12][13] . On the other hand, the frequency of CYP2C9*1*3 carriers in this study was much higher compared to earlier published data for Macedonians (10.3%), Serbians (12.04%), Croatians (12.78%), and Greeks (13.43%) [10][11][12][13] .…”

“…As for CYP2C9*1*2 carriers in our study, the percentage was slightly decreased compared to previously published data for Macedonians (19.6%), Serbians (21.76%), Croatians (23.52%), and Greeks (20.14%) [10][11][12][13] . On the other hand, the frequency of CYP2C9*1*3 carriers in this study was much higher compared to earlier published data for Macedonians (10.3%), Serbians (12.04%), Croatians (12.78%), and Greeks (13.43%) [10][11][12][13] . In our study population, we detected only one PMs with CYP2C9*2*3 genotype (4%) as expected from the previously published data for Macedonians (1%) and Serbians (0.93%) [10,11] .…”

“…In our study, NMs with CYP2C9*1*1 genotype were the most prevalent (52%), which was similar to the data previously reported for Macedonians (57.8%) [10] . The prevalence of NMs in Serbians (62.03%), Croatians (59.72%) and Greeks (62.19%) is slightly higher compared to Macedonians [11][12][13] . IMs comprise 44% of our study population, out of which 28% have CYP2C9*1*3 genotype and the rest 16% have CYP2C9*1*2 genotype.…”

“…CYP2C9 genotype distribution among donors from MBMDR, Macedonian, Serbian, Croatian, and Greek populations[10][11][12][13] …”