Epigenetic biomarkers of cold and heat syndromes of rheumatoid arthritis: Combining DNA hydroxymethylation and mRNA-sequencing.
Epigenetic biomarkers of cold and heat syndromes of rheumatoid arthritis: Combining DNA hydroxymethylation and mRNA-sequencing.
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DOI：
10.1111/1756-185x.14480
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发表时间：
2023-02
影响因子：
2.5
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证是中医理论中对疾病属性的归纳。这通常被用来解释为什么同一种疾病的患者表现出不同的症状。寒热是证候的两种基本倾向，因此，寒热证的识别是类风湿关节炎（RA）中医诊断和治疗的关键。然而，传统的寒热辨证思维模式依赖于临床表现，不可避免地受到医生主观性的影响。因此，寻找客观的生物标志物对提高RA寒热证候的准确性具有重要意义。以往的研究发现类风湿关节炎寒证和热证在基因表达和功能上存在差异，提示不同证型具有独特的生物学基础。1，2然而，由于中医证候的生物学基础庞大而复杂，因此，利用现代技术构建“病-证-生物标志物”网络，既保留中医证候的特点，又提高证候识别的客观性和适用性，是一项具有挑战性的工作。DNA羟甲基化是近年来越来越受到关注的表观遗传学标志。作为甲基化和去甲基化之间的桥梁，DNA羟甲基化驱动去甲基化，表明基因转录表达的重新激活。3更重要的是，DNA羟甲基化对环境刺激敏感，在不同的环境刺激下，DNA羟甲基化修饰的状态能够发生变化，从而导致表型差异。4这一调控机制与中医“环境差异可打破寒热平衡，引起RA患者外在临床症状差异”的概念相一致，推测从DNA羟甲基化和基因转录水平探讨RA寒热证候表观遗传生物标志物是可行的。本研究的目的是通过DNA羟甲基化测序和转录组测序相结合的方法，鉴定类风湿关节炎寒热证的表观遗传生物标志物。本研究已通过云南中医药大学第一附属医院伦理审查
Syndrome (Zheng in Mandarin Chinese) is the induction of disease attributes in the theory of traditional Chinese medicine (TCM). This is often used to explain why patients with the same disease show different symptoms. Cold and heat represent the two basic tendencies of a syndrome; therefore, the identification of cold and heat syndromes is key to the diagnosis and treatment of rheumatoid arthritis (RA) according to TCM. However, a traditional thinking model of cold and heat syndromes identifies a reliance on the clinical manifestations, which is inevitably affected by the subjectivity of doctors. It is important to identify objective biomarkers to improve accuracy in the identification of cold and heat syndromes of RA. Previous studies have identified differences in gene expression and function between cold and heat syndromes of RA, suggesting that different syndromes possess a unique biological basis. 1, 2 However, the biological basis is large and complex; therefor constructing a “disease–syndrome–biomaker” network using modern technology to preserve the characteristics of TCM and also improve the objectivity and applicability in syndrome identification is challengingDNA hydroxymethylation is an epigenetic marker that has attracted increasing attention recently. As a bridge between methylation and demethylation, DNA hydroxymethylation drives demethylation, indicating the reactivation of gene transcriptional expression. 3 More importantly, DNA hydroxymethylation is sensitive to environmental stimuli, the state of DNA hydroxymethylation modification is able to change under different environmental stimuli, resulting in phenotypic differences. 4 This regulatory mechanism is consistent with the concept of TCM, whereby “environmental differences can break the balance between cold and heat, causing differences in external clinical symptoms in patients with RA”, inferring that it is feasible to explore the epigenetic biomarkers of cold and heat syndromes of RA from DNA hydroxymethylation and gene transcription. The aim of our study was to identify epigenetic biomarkers of cold and heat syndromes of RA by combining DNA hydroxymethylation sequencing and transcriptome sequencing. Our study was approved through ethical review by the First Affiliated Hospital of Yunnan University of Traditional