Nilanjana Ghosh, Swati Srivastava, B. Kumari, I. Garg
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引用次数: 0
摘要
DNA 甲基化是基因表达的主要控制者之一,它不仅是引发癌症、阿尔茨海默病、帕金森病等多种疾病的原因。它还是冠状动脉疾病(CAD)、动脉粥样硬化、中风、心肌病等多种心血管疾病病理生理学的积极贡献者。核 DNA 甲基化在 VTE 中的作用早前已有研究,但对高海拔 VTE(HA-VTE)和海平面 VTE(SL-VTE)患者的核基因和线粒体基因的甲基化比较还没有深入研究。本研究获得了五名高海拔 VTE 患者和五名海平面 VTE 患者线粒体编码基因和核编码基因的 DNA 甲基化模式。在比较 HA-VTE 与 SL-VTE 的甲基化情况时,观察到 120 个高甲基化基因和 138 个低甲基化基因。经过基因富集和本体研究,发现 TCA 循环和 NADH 脱氢酶是两个研究组中富集程度较高的通路。使用 STRING 的蛋白质-蛋白质相互作用网络指出,当两个基因组都被富集时,L-2-羟基戊二酸的途径也被富集。这些结果表明线粒体DNA甲基化在血栓形成的病理生理学中起着至关重要的作用,并显示出研究线粒体在血栓形成中的作用的巨大潜力。
Altered Mitochondrial DNA Methylation Patterns in Thrombosis
DNA methylation being one of the chief controllers of gene expression has not only been the reason behind the initiation of a plethora of diseases like Cancer, Alzheimer’s disease, Parkinson’s disease, etc. Still, it is an active contributor to the pathophysiology of several cardiovascular diseases like coronary artery disease (CAD), Atherosclerosis, Stroke, Cardiomyopathy, etc. The role of nuclear DNA methylation in VTE has been studied earlier, but the comparison of methylation in both nuclear genes and mitochondrial genes in high altitude VTE (HA-VTE) and sea level VTE (SL-VTE) patients has not been studied in depth. Through this present study, DNA methylation patterns of mitochondrial encoded as well as nuclear-encoded mitochondrial genes of five high-altitude VTE patients and five sea-level VTE patients have been obtained. On comparing HA-VTE vs. SL-VTE methylation, one hundred and twenty hypermethylated genes and one hundred and thirty-eight hypomethylated genes were observed. Post gene enrichment and ontology study, the TCA cycle and NADH dehydrogenase were found to be the highly enriched pathways in both the study groups. Protein-protein interaction network using STRING pointed out the enriched pathway of L-2-hydroxyglutaric acid when both the gene sets were enriched. These results show the crucial role of mitochondrial DNA methylation in the pathophysiology of thrombosis and show great potential to study the role of mitochondria in thrombosis.