DNA Damage in Rheumatoid Arthritis: An Age-Dependent Increase in the Lipid Peroxidation-Derived DNA Adduct, Heptanone-Etheno-2′-Deoxycytidine

Objective . To evaluate what types of DNA damages are detected in rheumatoid arthritis (RA). Methods . The DNA adducts such as 8-oxo-hydroxy-7,8-dihydro-2′-deoxyguanosine (8-oxo-dG), 1,N 6 -etheno-2′-deoxyadenosine ( ε dA), and heptanone-etheno-2′-deoxycytidine (H ε dC) in genomic DNAs, derived from whole blood cells from 46 RA patients and 31 healthy controls, were analyzed by high-performance liquid chromatography tandem mass spectrometry, and their levels in RA patients and controls were compared. In addition, correlation between DNA adducts and clinical parameters of RA was analyzed. Results . Compared with controls, the levels of H ε dC in RA were significantly higher ( P < 0.0001) and age dependent ( r = 0.43, P < 0.01), while there was no significant difference in 8-oxo-dG and ε dA accumulation between RA patients and controls. H ε dC levels correlated well with the number of swollen joints ( r = 0.57, P < 0.0001) and weakly with the number of tender joints ( r = 0.26, P = 0.08) of RA patients, while they did not show a significant association with serological markers such as C-reactive protein and matrix metalloproteinase 3. Conclusion . These findings indicate that H ε dC may have some influence on the development of RA and/or its complications.