RNA-Based Biomarkers of Iron Metabolism in Dried Blood Spots for Detecting Recombinant Human Erythropoietin in Doping Control.

IF 2.6 3区医学 Q2 BIOCHEMICAL RESEARCH METHODS

Drug Testing and Analysis Pub Date : 2025-02-20 DOI:10.1002/dta.3870

Xiao Liu, Tiantian Yan, Yitong Xu, Xiaoci Zheng, Die Wu

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引用次数: 0

Abstract

Erythropoietin (EPO) abuse in sports has been a major challenge in doping analysis for decades. Although the Athlete Biological Passport (ABP) serves as an indirect method for EPO detection, it requires continual improvement to increase its sensitivity and reliability. Biomarkers related to iron metabolism and erythropoiesis as complementary parameters to enhance the ABP hematology module have the potential to improve its ability to detect EPO indirectly. In this study, RNA was extracted from dried blood spot (DBS) samples collected over 28 days (days 0, 1, 3, 5, 7, 9, 11, 13, 21, and 28) following the administration of therapeutic doses of recombinant human EPO (Yibiao, 50 IU/kg per dose, administered subcutaneously twice). The expression of four genes, namely, mitoferrin 1 (MFRN1), ferrochelatase (FECH), ferroportin (FPN), and ferritin heavy chain (FTH), was analyzed. The results revealed significant expression changes, with MFRN1 demonstrating peak increases of 2.43-fold, and presented detection windows extending beyond Day 9, providing greater sensitivity and longer detection windows than traditional ABP parameters do. The integration of MFRN1 into the ABP framework has the potential to increase the detection of EPO misuse in athletes.

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基于rna的干血斑铁代谢生物标志物检测重组人促红细胞生成素兴奋剂

几十年来，体育运动中红细胞生成素（EPO）的滥用一直是兴奋剂分析的主要挑战。虽然运动员生物护照（ABP）作为EPO检测的间接方法，但需要不断改进以提高其灵敏度和可靠性。与铁代谢和红细胞生成相关的生物标志物作为补充参数增强ABP血液学模块，有可能提高其间接检测EPO的能力。在本研究中，在给予治疗剂量的重组人促红细胞生成素（一标，每剂量50 IU/kg，皮下给药两次）后，在28天（0、1、3、5、7、9、11、13、21和28天）收集的干血斑（DBS）样本中提取RNA。分析丝裂铁蛋白1 （MFRN1）、铁螯合酶（FECH）、铁转运蛋白（FPN）和铁蛋白重链（FTH） 4个基因的表达情况。结果显示了显著的表达变化，MFRN1的峰值增加了2.43倍，并且检测窗口超过了第9天，比传统的ABP参数提供了更高的灵敏度和更长的检测窗口。将MFRN1整合到ABP框架中有可能增加运动员中EPO滥用的检测。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Drug Testing and Analysis BIOCHEMICAL RESEARCH METHODS-CHEMISTRY, ANALYTICAL

CiteScore

5.90

自引率

24.10%

发文量

191

审稿时长

2.3 months

期刊介绍： As the incidence of drugs escalates in 21st century living, their detection and analysis have become increasingly important. Sport, the workplace, crime investigation, homeland security, the pharmaceutical industry and the environment are just some of the high profile arenas in which analytical testing has provided an important investigative tool for uncovering the presence of extraneous substances. In addition to the usual publishing fare of primary research articles, case reports and letters, Drug Testing and Analysis offers a unique combination of; ‘How to’ material such as ‘Tutorials’ and ‘Reviews’, Speculative pieces (‘Commentaries’ and ‘Perspectives'', providing a broader scientific and social context to the aspects of analytical testing), ‘Annual banned substance reviews’ (delivering a critical evaluation of the methods used in the characterization of established and newly outlawed compounds). Rather than focus on the application of a single technique, Drug Testing and Analysis employs a unique multidisciplinary approach to the field of controversial compound determination. Papers discussing chromatography, mass spectrometry, immunological approaches, 1D/2D gel electrophoresis, to name just a few select methods, are welcomed where their application is related to any of the six key topics listed below.