通常与抗逆转录病毒治疗代谢相关的单核苷酸多态性的药理学效应

A. Bazhenova, K. Mironov, A. Kravchenko, V. Akimkin
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引用次数: 0

摘要

介绍确定抗逆转录病毒疗法(ART)的药物遗传学效应已成为推进HIV阳性患者个性化治疗的一个重要里程碑。这些治疗方案伴随着多种副作用。治疗效果和不良反应可能由个体遗传易感性因素决定,最佳处方应考虑这些因素。一些遗传标记物(HLA-B*57:01和UGT1A1*28)已经被证明可以提高停药率,并努力扩大临床相关基因测试的范围。客观的在这篇综述中,介绍了基因多态性及其对确定患者抗逆转录病毒疗法耐受性的影响的最新综述。本研究的目的是评估编码参与ART代谢和转运的蛋白质的基因中存在的单核苷酸多态性(SNPs)。这篇综述将用于开发一种基于PCR的检测方法,用于检测和确认高加索人群中的风险等位基因。材料和方法。对46篇原始研究论文和综述的数据进行了分析。将最相关多态性的等位基因频率与欧洲人群的数据进行核对。后果作为这篇综述的结果,选择了一些最有前途的SNP进行未来的研究。首先,ABCC4 rs1751034和rs3741206以及ABCC10 rs9349256和rs2125739在接受替诺福韦治疗时与肾损伤风险增加、血浆浓度升高和毒性增加有关。ABCC4和ABCC10 SNP对肾损伤的影响以及最近报道的作为潜在肾毒性标志物的CYP24A1 rs2248359的平行分析可能会提供更多信息。其次,应评估与依非韦伦血浆浓度增加以及肝脏和中枢神经系统毒性风险增加相关的CYP2B6 rs3745274。CYP2B6、CYP2A6(rs28399433)和CYP3A4(rs4646437)中的SNPs应同时进行评估,因为拥有这三种变体可能会使患者面临更高的风险。结论如果在高加索人群中发现显著影响,已识别的等位基因可能会成为药物处方方案中使用的新标记。应测试最相关的SNPs,以支持未来的研究,评估其对俄罗斯HIV患者的意义。
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Pharmacogenetic effects of single nucleotide polymorphisms commonly associated with antiretroviral therapy metabolism
Introduction. Identification of pharmacogenetic effects on antiretroviral therapy (ART) has become an important milestone to reach in the advancement of personalised treatment for HIV-positive patients. The therapy schemes are accompanied by multiple side effects. Therapy effectiveness and adverse reactions can be dictated by individual genetic predisposition factors, which should be taken into account for an optimal prescription. Some genetic markers (HLA-B*57:01 and UGT1A1*28), were already proven to improve discontinuation rates, and efforts are allocated to expand the range of clinically-relevant genetic tests.Objective. In this review, an updated summary of genetic polymorphisms and their effects defining patients’ tolerability to ART is presented. The aim of this research is to assess single nucleotide polymorphisms (SNPs) present in the genes that encode proteins involved in ART metabolism and transport. This review will be used to develop a PCR-based testing methodology for the detection and confirmation of risk alleles in the Caucasian population.Materials and methods. Data from 46 original research papers and reviews was analysed. Allele frequencies of the most relevant polymorphisms were checked against the data for European population.Results. As an outcome of this review, a few most promising SNPs were selected for future research. Firstly, ABCC4 rs1751034 and rs3742106 and ABCC10 rs9349256 and rs2125739 were associated with an increased risk of renal impairment, higher plasma concentration, and toxicity when treated with tenofovir. Parallel analysis of ABCC4 and ABCC10 SNP effects on renal impairment together with CYP24A1 rs2248359 that was recently reported as a potential renal toxicity marker might be more informative. Secondly, CYP2B6 rs3745274 that was associated with an increased efavirenz plasma concentration, and increased risk of liver and CNS toxicity should be evaluated. SNPs in CYP2B6, CYP2A6 (rs28399433), and CYP3A4 (rs4646437) should be evaluated in parallel since possession of all three variants might put patients at a much higher risk.Conclusion. Identified alleles could become new markers used in drug prescription protocols if significant effect in Caucasian population will be found. The most relevant SNPs should be tested in in supporting future studies to evaluate the significance for patients with HIV in Russia.
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来源期刊
HIV Infection and Immunosuppressive Disorders
HIV Infection and Immunosuppressive Disorders Medicine-Infectious Diseases
CiteScore
0.70
自引率
0.00%
发文量
37
期刊介绍: In the scientific-practical journal "HIV Infection and Immunosuppressive Disorders", published various issues of HIV medicine (epidemiology, molecular mechanisms of pathogenesis to the development of educational programs) leading scientists of Russia and countries of CIS, USA, as well as practical healthcare professionals working in research centers, research institutes, universities, clinics where done basic medical work. A special place on the pages of the publication is given to basic and clinical research, analytical reviews of contemporary and foreign reports, the provision of medical care for various diseases.
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