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波黑塞族共和国人群中五种药理学上最重要的等位基因变体的流行情况。

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

机构信息

University of Banja Luka Faculty of Medicine, Department of Human Genetics, Banja Luka, Bosnia and Herzegovina.

University of Banja Luka Faculty of Medicine, Centre for Biomedical Research, Laboratory for Molecular Biology and Genetics, Banja Luka, Bosnia and Herzegovina.

出版信息

Arh Hig Rada Toksikol. 2021 Jun 28;72(3):129-134. doi: 10.2478/aiht-2021-72-3499.

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 and 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 and 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 and 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 and should be taken into consideration to minimise individual risk and improve benefits of drug therapy in the Republic of Srpska.

摘要

细胞色素 P450 超家族的酶在 I 相药物代谢中起着关键作用。其中,CYP2C9 和 CYP2C19 具有重要的临床意义,因为它们可以介导严重的毒性、治疗失败以及对化学物质引起的癌症和其他疾病的易感性增加。本研究旨在确定斯普斯卡共和国(波斯尼亚和黑塞哥维那)普通人群中 和 基因中具有药理学重要性的等位基因变异的流行率,并将其与其他人群进行比较。为此,我们使用实时聚合酶链反应(RT-PCR)确定了 216 名随机选择的健康志愿者的基因型谱和等位基因频率。和 等位基因的流行率分别为 13.6%和 7.4%。根据这些频率,在 216 名参与者中,有 4 名(1.86%)被预测为代谢不良者,78 名(36.11%)为中间代谢者,其余 134 名(62.03%)为正常代谢者。根据 和 变体的流行率 - 分别为 16.2%和 20.4% - 有 9 名(4.17%)被预测为代谢不良者,57 名(26.39%)为快速代谢者,9 名(4.17%)为超快代谢者。我们发现我们的人群与来自其他欧洲国家的人群的等位基因频率没有显著差异。这些发现表明,应考虑 和 基因的遗传决定表型,以最大程度地降低个体风险并提高斯普斯卡共和国的药物治疗效益。

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