Role of mitochondrial sirtuins in rheumatoid arthritis

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.