Department of Rheumatology, National University of Medical Sciences, Rawalpindi, Pakistan; Department of Rheumatology, Pak Emirates Military Hospital, Rawalpindi, Pakistan.
Cancer Genetics and Epigenetics Lab, Department of Biosciences COMSATS University, Islamabad, Pakistan.
Biochem Biophys Res Commun. 2021 Dec 20;584:60-65. doi: 10.1016/j.bbrc.2021.11.016. Epub 2021 Nov 6.
Current study is intended to evaluate the expression and epigenetic variations of mitochondrial situins in 306 rheumatoid arthritis (RA) cases and compared with age/gender matched controls.
The expression level was measured using the quantitative Real time PCR (qPCR) and epigenetic analysis was performed by measuring deacetylation activity. Oxidative stress was also measured in present study using the enzyme linked immunoassay (ELISA). The obtained results were evaluated by means of the student t-test, spearman correlation and ROC curve analysis.
Expression analysis showed the significant downregulation of SIRT3 (p < 0.0001), SIRT4 (p < 0.0001) and SIRT5 (p < 0.0001) in RA cases when compared with controls. Downregulation of mitochondrial sirtuins was significantly associated with positive anti-CCP status, increased ESR level and with increased CRP levels. Epigenetic analysis showed significant increased histone deacetylation in RA patients compared to controls. Co-expression analysis showed the significant negative association between expression level of mitochondrial sirtuins and deacytylation level (SIRT3 r = -0.438, p < 0.0001; SIRT4 r = -0.424, p < 0.0001; SIRT5 r = -0.282, p < 0.0001). ROC curve analysis exhibited that downregulation of mitochondrial sirtuins (SIRT3 AUC = 0.91, p < 0.001; SIRT4 AUC = 0.92, p < 0.001; SIRT5 AUC = 0.85, p < 0.001) was act as the good diagnostic marker for detection/diagnosis of arthritis.
The results show that significant deregulation of mitochondrial sirtuins was associated with increased arthritis risk and can be act as an indicator of advance clinical outcome.
本研究旨在评估线粒体 situin 在 306 例类风湿关节炎（RA）病例中的表达和表观遗传变化，并与年龄/性别匹配的对照进行比较。
使用定量实时 PCR（qPCR）测量表达水平，并通过测量去乙酰化活性进行表观遗传分析。本研究还使用酶联免疫吸附试验（ELISA）测量氧化应激。通过学生 t 检验、斯皮尔曼相关性和 ROC 曲线分析评估获得的结果。
表达分析表明，与对照组相比，RA 病例中 SIRT3（p < 0.0001）、SIRT4（p < 0.0001）和 SIRT5（p < 0.0001）的表达明显下调。线粒体 sirtuins 的下调与抗 CCP 阳性状态、ESR 水平升高和 CRP 水平升高显著相关。表观遗传分析显示，RA 患者的组蛋白去乙酰化水平明显高于对照组。共表达分析显示，线粒体 sirtuins 的表达水平与去乙酰化水平呈显著负相关（SIRT3 r = -0.438，p < 0.0001；SIRT4 r = -0.424，p < 0.0001；SIRT5 r = -0.282，p < 0.0001）。ROC 曲线分析表明，线粒体 sirtuins 的下调（SIRT3 AUC = 0.91，p < 0.001；SIRT4 AUC = 0.92，p < 0.001；SIRT5 AUC = 0.85，p < 0.001）可作为关节炎检测/诊断的良好诊断标志物。
结果表明，线粒体 sirtuins 的显著失调与关节炎风险增加有关，并可作为预示临床预后的指标。
