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土耳其人群中CYP2C9、CYPC19和CYP2D6基因谱以及药物反应和毒性的基因易感性

CYP2C9, CYPC19 and CYP2D6 gene profiles and gene susceptibility to drug response and toxicity in Turkish population.

作者信息

Arici Merve, Özhan Gül

机构信息

Istanbul University, Faculty of Pharmacy, Department of Pharmaceutical Toxicology, Beyazit, 34116 Istanbul, Turkey.

出版信息

Saudi Pharm J. 2017 Mar;25(3):376-380. doi: 10.1016/j.jsps.2016.09.003. Epub 2016 Sep 17.

Abstract

Pharmacogenetics is a vast field covering drug discovery research, the genetic basis of pharmacokinetics and dynamics, genetic testing and clinical management in diseases. Pharmacogenetic approach usually focuses on variations of drug transporters, drug targets, drug metabolizing enzymes and other biomarker genes. Cytochrome P450 (CYP) enzymes, an essential source of variability in drug-response, play role in not only phase I-dependent metabolism of xenobiotics but also metabolism of endogenous compounds such as steroids, vitamins and fatty acids. CYP2C9, CYP2C19 and CYP2D6 enzymes being highly polymorphic are responsible for metabolism of a variety of drug groups. In the study, it was determined the genotype and allele frequency of and very common and functional single-nucleotide polymorphisms (SNPs), in healthy volunteers. The genotype distributions were consistent with the Hardy-Weinberg equilibrium in the population ( > 0.05). It is believed that the determination of polymorphisms in the enzymes may be beneficial in order to prevention or reduction in adverse effects and death. The recessive allele frequencies of and were 11, 13, 12, 13, 25, 4 and 15%, respectively. According to the obtained results, the carriers of variant allele should be received higher doses of the drugs metabolizing with this enzyme in Turkish population, while the carriers of other variant alleles do not generally have any requirement of dose regimen.

摘要

药物遗传学是一个广阔的领域,涵盖药物发现研究、药代动力学和药效学的遗传基础、基因检测以及疾病的临床管理。药物遗传学方法通常聚焦于药物转运体、药物靶点、药物代谢酶和其他生物标志物基因的变异。细胞色素P450(CYP)酶是药物反应变异性的重要来源,不仅在异源生物的I相依赖性代谢中起作用,还参与类固醇、维生素和脂肪酸等内源性化合物的代谢。高度多态的CYP2C9、CYP2C19和CYP2D6酶负责多种药物组的代谢。在该研究中,测定了健康志愿者中非常常见且具有功能的单核苷酸多态性(SNP)的基因型和等位基因频率。基因型分布符合群体中的哈迪-温伯格平衡(>0.05)。人们认为,测定这些酶中的多态性可能有助于预防或减少不良反应和死亡。[具体基因名称]的隐性等位基因频率分别为11%、13%、12%、13%、25%、4%和15%。根据所得结果,在土耳其人群中,[具体基因名称]变异等位基因的携带者在使用该酶代谢的药物时应接受更高剂量,而其他变异等位基因的携带者通常对剂量方案没有任何特殊要求。

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