Genetic polymorphisms of cytochrome P450 enzymes: CYP2C9, CYP2C19, CYP2D6, CYP3A4, and CYP3A5 in the Croatian population

Ganoci, Lana; Božina, Tamara; Skvrce, Nikica Mirošević; Lovrić, Mila; Mas, Petar; Božina, Nada

doi:10.1515/dmpt-2016-0024

Cited by 29 publications

(27 citation statements)

References 60 publications

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“…Our findings of the CYP2C19*17 frequency in Kosovars are very similar to reports from the neighbouring countries, Greece (19.61 %, p=0.69) and Macedonia (20.2 %; p=0.84) in particular (23,24,31). In Caucasians its frequency varies from 15.4 % to 20.2 % (17).…”

Section: Cyp2c19supporting

confidence: 88%

“…This finding corresponds to the other reports for Caucasians (18,24,28), as it varies from 85 to 96 % (38). The CYP3A5*3 allele plays an important role in the pharmacokinetics of tacrolimus (basic therapy for immunosuppression in patients who undergo solid organ and haematopoietic stem cell transplantation) and imatinib (a tyrosine kinase inhibitor, which is the drug of choice in treating blood malignancies such as chronic myeloid leukaemia) (39).…”

Section: Cyp3a5supporting

confidence: 87%

“…The frequency of CYP2C9 poor metabolisers was 6.8 %, which is similar to the Spanish (5.0 %) (16) and Macedonian (5.1 %) population, but differs from England's population (3.2 %) (17,18). The following frequencies of CYP2C9*2 have been reported for the European Mediterranean and other European countries: Spain (16.0 %), Greece (12.9 %), Croatia (14.0 %), Romania (11.3 %), Germany (14.0 %), France (15.0 %), and Sweden (10.7 %) (19)(20)(21)(22)(23)(24)(25). CYP2C9*3 has the highest prevalence in Southern Asian populations (10.1 %) (25), while in the Western, Central, and Southeastern Europe it is present in …”

Section: Cyp2c9mentioning

confidence: 95%

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Genetic polymorphisms of CYP2C9, CYP2C19, and CYP3A5 in Kosovar population

Krasniqi

Dimovski

Bytyqi

et al. 2017

Archives of Industrial Hygiene and Toxicology

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Cytochrome P450 genetic polymorphisms are responsible for individual variations in drug metabolism and drug-drug interactions. They are very important for pharmacogenetics, and their frequency varies across different populations. There is a big gap in the knowledge about the CYP gene family polymorphisms in the population of Kosovo, and the aim of our study was to fill that gap by determining the frequency of the most important variant alleles of CYP2C9, CYP2C19, and CYP3A5 in 234 nonrelated Kosovars. The allele frequencies of CYP2C9*2 and 2C9*3 were 17.52 %, and 10.89 %, respectively. Sixteen participants (6.81 %) were CYP2C9 poor metabolisers. The CYP2C19*2 and *17 variant frequencies were 13.03 % and 19.01 %, respectively. There were 2.13 % CYP2C19 poor and 4.27 % ultra-rapid metabolisers (homozygous carriers of the *17 allele). With regard to CYP3A5, the frequency of the *3 variant allele was 98.29 % (non-expressors), while the remaining participants (1.70 %) were expressors of CYP3A5. These findings are comparable with other European ethnicities, specifically those of Southeast Europe. KEY WORDS: cytochrome P450 enzyme system; drug metabolism; pharmacogeneticsIndividual variability in response to the most common drugs presents one of the major challenges to pharmacotherapy today. This variability depends on a variety of factors (drug interactions, hepatorenal disorders, sex, age, and lifestyle), but the most challenging are the genetic polymorphisms that have a direct and important impact on drug-detoxifying enzymes, drug targets, and drug transporters (1-3). Phase I enzymes metabolise nearly 59 % of the drugs reported for adverse drug reactions (ADR), and cytochromes P450 (CYP450 or CYP) make 75-86 % of these phase I enzymes (2, 4). Their genetic variants are responsible for unintended drug metabolism and interactions (5) that can lead to toxicity or failed pharmacotherapy (6). This has been recognised by the US Food and Drug Administration (FDA) and European Medicines Agency (EMA), as both push policies requiring that pharmacogenetic information is provided for drug development and postmarketing surveillance (7,8).The most important genetic variants of CYP in clinical practice include those of CYP2C9, CYP2C19, and CYP3A5. Their frequencies vary across populations, and mapping them, so to speak, can be very useful in designing specific pharmacotherapy. To the best of our knowledge no such mapping has been done for the population of Kosovo, a southeast European country of over 1.7 million people, 93 % of whom are ethnic Albanians. The aim of our study was to address this gap and determine the frequency of the pharmacologically most important variant alleles of CYP2C9, CYP2C19, and CYP3A5 in Kosovo population, hoping that our findings could help to optimise pharmacotherapy in the country. PARTICIPANTS AND METHODSThis study included a mixed population of 234 randomly selected Caucasians (116 women and 118 men) with no blood relation from all parts of Kosovo. Their age ranged between 18 and 65 years (median: 3...

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Section: Cyp2c19supporting

confidence: 88%

Section: Cyp3a5supporting

confidence: 87%

Section: Cyp2c9mentioning

confidence: 95%

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Genetic polymorphisms of CYP2C9, CYP2C19, and CYP3A5 in Kosovar population

Krasniqi

Dimovski

Bytyqi

et al. 2017

Archives of Industrial Hygiene and Toxicology

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“…Based on previous investigations in the target population , we expected frequency of the variant allele at MDR1/ABCB1 1236C>T to be around 40% and frequency of intermediate or slow CYP2C9 or CYP2C19 metabolizers to be around 20–30%. Since we had no insight into the frequency of variant alleles at other genotyped loci, which might be ethnically specific, we opted not to define the sample size on an a priori power calculation but reasoned that subjects should be enrolled until the smallest treatment‐by‐variant allele carriage subset included at least 10 subjects.…”

Section: Methodsmentioning

confidence: 99%

Interaction betweenABCG2 421C>Apolymorphism and valproate in their effects on steady‐state disposition of lamotrigine in adults with epilepsy

Domjanović

Lovrić

Trkulja

et al. 2018

Brit J Clinical Pharma

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“…To date, at least 28 alleles of CYP2C19 have been identified, and there are ethnic and geographical differences in the distribution of CYP2C19 variants (Kurose et al, 2012). When compared with Caucasian and African populations, CYP2C19 Ã 1 allele (wild-type) frequency was significantly lower, while the frequency of CYP2C19 Ã 3 allele was higher in the Chinese Han subjects (Ganoci et al, 2017;Masimirembwa et al, 1995). Zhou et al (2009) compared allele frequencies of Han samples (Beijing) with five other geographical subpopulations of Han Chinese (Hong Kong, Shanghai, Shantou, Shenyang and Xi'an) and observed that the frequencies of CYP2C19 Ã 1, Ã 2 and Ã 3 were significantly different from that of Shengyang and Xi'an subpopulations.…”

Section: Clopidogrel Metabolism Phenotypementioning

confidence: 99%

Comparison between MassARRAY and pyrosequencing for CYP2C19 and ABCB1 gene variants of clopidogrel efficiency genotyping

Liu

et al. 2019

Molecular Membrane Biology

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Clopidogrel is one of the most frequently used drugs in patients to reduce cardiovascular events. Since patients with different genetic variations respond quite differently to clopidogrel therapy, the related genetic testing plays a vital role in its dosage and genetic testing related to clopidogrel therapy is currently considered as routine test worldwide. In this study, we aim to use two different methods MALDI-TOF mass spectrometry and pyrosequencing to detect gene variant of CYP2C19 and ABCB1. Six single nucleotides polymorphisms (SNP) within CYP2C19 (Ã 2, Ã 3, Ã 4, Ã 5, Ã 17) and ABCB1 C3435T in 458 Chinese Han patients were determined using both MassARRAY and Pyrosequencing. Sanger sequencing was used for verification. Results of both methods were analyzed and compared. Allele frequencies of each SNP and distribution of different genotypes were calculated based on the MassARRAY and Sanger sequencing results. Both methods provided 100% call rates for gene variants, while results of six samples were different with two methods. With Sanger sequencing as the reference results, MassARRAY generated all the same results. The minor allele frequencies of the above six SNPs were 27.1% (CYP2C19 Ã), 5.9% (CYP2C19 Ã 3), 0% (CYP2C19 Ã 4), 0% (CYP2C19 Ã 5), 1.1% (CYP2C19 Ã 17), 40.9% (ABCB1), respectively. MassARRAY provides accurate clopidogrel related genotyping with relatively high cost-efficiency, throughput and short time when compared with pyrosequencing.

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Genetic polymorphisms of cytochrome P450 enzymes: CYP2C9, CYP2C19, CYP2D6, CYP3A4, and CYP3A5 in the Croatian population

Abstract: The frequency of the CYP allelic variants, genotypes, and predicted phenotypes in the Croatian population is in accordance with the other European populations, between the values of published data for Middle European and Mediterranean populations.

Cited by 29 publications

References 60 publications

Genetic polymorphisms of CYP2C9, CYP2C19, and CYP3A5 in Kosovar population

Genetic polymorphisms of CYP2C9, CYP2C19, and CYP3A5 in Kosovar population

Interaction betweenABCG2 421C>Apolymorphism and valproate in their effects on steady‐state disposition of lamotrigine in adults with epilepsy

Comparison between MassARRAY and pyrosequencing for CYP2C19 and ABCB1 gene variants of clopidogrel efficiency genotyping

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