ABC药物转运蛋白的单核苷酸多态性改变暴露于暴露前预防的健康南非妇女中替诺福韦的表达和循环。

IF 16.4 1区化学 Q1 CHEMISTRY, MULTIDISCIPLINARY

Accounts of Chemical Research Pub Date : 2023-07-01 Epub Date: 2023-07-28 DOI:10.2217/pgs-2023-0058

Nomusa M Zondo, Parveen Sobia, Aida Sivro, Sinaye Ngcapu, Leila E Mansoor, Sharana Mahomed, Lara Lewis, Veron Ramsuran, Derseree Archary

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引用次数: 0

摘要

目的：我们研究了在服用Truvada®预防艾滋病毒的南非妇女中，ATP结合盒（ABC）药物转运蛋白中的单核苷酸多态性（SNPs）是否会改变基因表达和替诺福韦的处置。材料与方法：在393名女性中，使用实时PCR来确定ABC转运蛋白基因中的6个SNPs、mRNA表达和循环替诺福韦之间的相关性。结果：单变量和多变量分析显示，ABCC4（3463C/T）SNP的CT和TT基因型相对于CC基因型具有显著更高的替诺福韦水平。相反，ABCC4（4976A/G）SNP的AA基因型显示替诺福韦显著减少，而mRNA表达增加。结论：ABCC4基因中的SNPs可能对基因表达和替诺福韦循环产生不同的影响。它们的影响可能为暴露前预防效果低提供信息，并在富含某些基因型的非洲妇女的临床试验中发现有效药物。

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Single-nucleotide polymorphisms in ABC drug transporters alter expression and circulating tenofovir in healthy South African women exposed to pre-exposure prophylaxis.

Aim: We investigated if single-nucleotide polymorphisms (SNPs) in ATP-binding cassette (ABC) drug transporters alter gene expression and tenofovir disposition in South African women taking Truvada^® for HIV prevention. Materials & methods: In 393 women, real-time PCR was used to determine the associations between six SNPs in ABC transporter genes, mRNA expression and circulating-tenofovir. Results: Univariable and multivariable analyses showed that CT and TT relative to CC genotypes for the ABCC4(3463C/T) SNP had significantly higher tenofovir levels. In contrast, the AA genotype for the ABCC4(4976A/G) SNP showed significantly less tenofovir, while mRNA expression was increased. Conclusion: SNPs in the ABCC4 gene may differentially affect gene expression and circulating tenofovir. Their impact may inform on low pre-exposure prophylaxis efficacy and discern effective drugs in clinical trials of African women enriched for certain genotypes.

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来源期刊

Accounts of Chemical Research 化学-化学综合

CiteScore

31.40

自引率

1.10%

发文量

312

审稿时长

2 months

期刊介绍： Accounts of Chemical Research presents short, concise and critical articles offering easy-to-read overviews of basic research and applications in all areas of chemistry and biochemistry. These short reviews focus on research from the author’s own laboratory and are designed to teach the reader about a research project. In addition, Accounts of Chemical Research publishes commentaries that give an informed opinion on a current research problem. Special Issues online are devoted to a single topic of unusual activity and significance. Accounts of Chemical Research replaces the traditional article abstract with an article "Conspectus." These entries synopsize the research affording the reader a closer look at the content and significance of an article. Through this provision of a more detailed description of the article contents, the Conspectus enhances the article's discoverability by search engines and the exposure for the research.