基于MALDI-TOF MS的SNP测定用于确定适合中国患者的抗抑郁药物

IF 3.1 3区 医学 Q2 CHEMISTRY, ANALYTICAL
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引用次数: 0

摘要

药物仍然是抑郁症的首选主要治疗方法,尽管有些患者在接受药物治疗期间,在取得令人满意的临床疗效方面表现出显著的个体差异。基因多态性约占治疗反应个体差异的 40%。因此,本研究旨在开发一种技术,以鉴定与中国患者抗抑郁药物代谢、疗效和副作用相关的单核苷酸多态性(SNPs)。研究采用文献计量学方法,在 Web of Science 中检索与 "抑郁症 "和 "SNP "相关的文献。利用 PharmGKB 数据库对获得的 SNP 信息进行筛选。通过设计和优化引物并进行复合扩增系统,建立了一种基于 MALDI-TOF MS 的方法来检测与舍曲林、氟西汀、西酞普兰、艾司西酞普兰、文拉法辛、氟伏沙明、帕罗西汀和米氮平等抗抑郁药物相关的多态性。桑格测序验证了所建立方法的准确性和灵敏度。从数据库中共筛选出 10,043 篇文章,并从 PharmGKB 数据库中提取了 46 个在亚洲人群中突变频率为 >1 % 并注释了相关临床药物的 SNPs。该方法与 Sanger 测序结果进行了比较,检测结果的准确率为 100%。本研究中开发的基于 MALDI-TOF MS 的 SNP 检测方法可以快速、方便、有效地帮助患者找到适合自己的药物。此外,我们还发现这种SNP检测方法有望成为评估药物疗效个体化差异的潜在参考工具,不仅可以筛查患者服药后抗抑郁疗效不佳的原因,还可以指导医生了解药物疗效的个体化差异。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
MALDI-TOF MS-based SNP assay used to determine the appropriate antidepression for Chinese patients

Medicine remains the preferred primary treatment for depression, although some patients show remarkable individual variations in achieving satisfactory clinical outcomes during medication. Genetic polymorphisms cause approximately 40 % of individual differences in treatment response. Therefore, this study aimed to develop a technique to identify single nucleotide polymorphisms (SNPs) associated with the metabolism, effectiveness, and side effects of antidepressant medications in Chinese patients. Bibliometrics was used to search literature related to “depression” and “SNP” in Web of Science. The obtained SNP information was screened using the PharmGKB database. By designing and optimizing primers and conducting a compound amplification system, a method was established based on MALDI-TOF MS to detect polymorphisms associated with the antidepressant drugs, including sertraline, fluoxetine, citalopram, escitalopram, venlafaxine, fluvoxamine, paroxetine, and mirtazapine. The accuracy and sensitivity of the established method were verified by Sanger sequencing. A total of 10,043 articles were screened from the database, and 46 SNPs with a mutation frequency of >1 % in Asian populations and annotated with relevant clinical drugs were extracted from the PharmGKB database. This method was compared with the results of Sanger sequencing, and the accuracy of the detection results was 100 %. The MALDI-TOF MS-based SNP assay developed in this study can be a fast, convenient and effective way for patients to find the right medication for themselves. Moreover, we found that this SNP assay holds the promise of being a potential reference tool for assessing individualised differences in drug efficacy, not only for screening the causes of poor antidepressant efficacy in patients after taking medication, but also for advising physicians to understand individualised differences in drug efficacy.

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来源期刊
CiteScore
6.70
自引率
5.90%
发文量
588
审稿时长
37 days
期刊介绍: This journal is an international medium directed towards the needs of academic, clinical, government and industrial analysis by publishing original research reports and critical reviews on pharmaceutical and biomedical analysis. It covers the interdisciplinary aspects of analysis in the pharmaceutical, biomedical and clinical sciences, including developments in analytical methodology, instrumentation, computation and interpretation. Submissions on novel applications focusing on drug purity and stability studies, pharmacokinetics, therapeutic monitoring, metabolic profiling; drug-related aspects of analytical biochemistry and forensic toxicology; quality assurance in the pharmaceutical industry are also welcome. Studies from areas of well established and poorly selective methods, such as UV-VIS spectrophotometry (including derivative and multi-wavelength measurements), basic electroanalytical (potentiometric, polarographic and voltammetric) methods, fluorimetry, flow-injection analysis, etc. are accepted for publication in exceptional cases only, if a unique and substantial advantage over presently known systems is demonstrated. The same applies to the assay of simple drug formulations by any kind of methods and the determination of drugs in biological samples based merely on spiked samples. Drug purity/stability studies should contain information on the structure elucidation of the impurities/degradants.
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