Limits...
DNA damage in rheumatoid arthritis: an age-dependent increase in the lipid peroxidation-derived DNA adduct, heptanone-etheno-2'-deoxycytidine.

Ogawa M, Matsuda T, Ogata A, Hamasaki T, Kumanogoh A, Toyofuku T, Tanaka T - Autoimmune Dis (2013)

Bottom Line: Results.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.

View Article: PubMed Central - PubMed

Affiliation: Department of Respiratory Medicine, Allergy and Rheumatic Diseases, Osaka University Graduate School of Medicine, 2-2 Yamada-Oka, Suita, Osaka 565-0871, Japan.

ABSTRACT
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.

No MeSH data available.


Related in: MedlinePlus

HεdC levels are significantly elevated in RA patients. (a) The respective median (range) values of HεdC from RA patients and controls were 10.3 (0.3–119) and 0.33 (0.3–17.8) per 109 bases. HεdC levels in RA patients were thus significantly higher than in controls (P < 0.0001). The straight and dotted line represent linear approximation of the values of HεdC versus age from RA patients and controls. (b) The geographic mean level of HεdC increased with aging in RA patients (P = 0.003).
© Copyright Policy
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC3814043&req=5

fig3: HεdC levels are significantly elevated in RA patients. (a) The respective median (range) values of HεdC from RA patients and controls were 10.3 (0.3–119) and 0.33 (0.3–17.8) per 109 bases. HεdC levels in RA patients were thus significantly higher than in controls (P < 0.0001). The straight and dotted line represent linear approximation of the values of HεdC versus age from RA patients and controls. (b) The geographic mean level of HεdC increased with aging in RA patients (P = 0.003).

Mentions: The results for 8-oxo-dG and εdA are shown in Figure 2. The median (range) levels of 8-oxo-dG per 109 bases in RA patients and controls are 176.4 (52.5–449) and 127.1 (58.1–372), respectively, and they did not differ. Moreover, there was no significant difference in εdA between the two groups, RA: 29 (2.6–1635) (median (range)) per 109 bases versus control: 34.7 (0.2–121) per 109 bases. Four patients with RA showed an increase in εdA accumulation, but no association was detected between these values and disease activity parameters such as CRP and the number of involved joints. However, HεdC levels were significantly higher in RA patients, 10.3 (0.3–119) (median (range)) per 109 bases than those in controls, 0.33 (0.3–17.8) per 109 bases (P < 0.0001) (Figure 3(a)), and this significance was observed in all age-interval analyses (mean ratio at 35: P = 0.0009; for other age intervals: P < 0.0001) as shown in Figure 3(b), and the mean of level of the adduct HεdC in RA patients was approximately five times higher than that in controls. Moreover, in order to match the number of sex between RA patients and controls, the datum of 14 women and 7 men were randomly selected, and it was confirmed that HεdC (but not 8-oxo-dG and εdA) levels were significantly higher in RA patients than those in controls (P < 0.0001, data not shown).


DNA damage in rheumatoid arthritis: an age-dependent increase in the lipid peroxidation-derived DNA adduct, heptanone-etheno-2'-deoxycytidine.

Ogawa M, Matsuda T, Ogata A, Hamasaki T, Kumanogoh A, Toyofuku T, Tanaka T - Autoimmune Dis (2013)

HεdC levels are significantly elevated in RA patients. (a) The respective median (range) values of HεdC from RA patients and controls were 10.3 (0.3–119) and 0.33 (0.3–17.8) per 109 bases. HεdC levels in RA patients were thus significantly higher than in controls (P < 0.0001). The straight and dotted line represent linear approximation of the values of HεdC versus age from RA patients and controls. (b) The geographic mean level of HεdC increased with aging in RA patients (P = 0.003).
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3814043&req=5

fig3: HεdC levels are significantly elevated in RA patients. (a) The respective median (range) values of HεdC from RA patients and controls were 10.3 (0.3–119) and 0.33 (0.3–17.8) per 109 bases. HεdC levels in RA patients were thus significantly higher than in controls (P < 0.0001). The straight and dotted line represent linear approximation of the values of HεdC versus age from RA patients and controls. (b) The geographic mean level of HεdC increased with aging in RA patients (P = 0.003).
Mentions: The results for 8-oxo-dG and εdA are shown in Figure 2. The median (range) levels of 8-oxo-dG per 109 bases in RA patients and controls are 176.4 (52.5–449) and 127.1 (58.1–372), respectively, and they did not differ. Moreover, there was no significant difference in εdA between the two groups, RA: 29 (2.6–1635) (median (range)) per 109 bases versus control: 34.7 (0.2–121) per 109 bases. Four patients with RA showed an increase in εdA accumulation, but no association was detected between these values and disease activity parameters such as CRP and the number of involved joints. However, HεdC levels were significantly higher in RA patients, 10.3 (0.3–119) (median (range)) per 109 bases than those in controls, 0.33 (0.3–17.8) per 109 bases (P < 0.0001) (Figure 3(a)), and this significance was observed in all age-interval analyses (mean ratio at 35: P = 0.0009; for other age intervals: P < 0.0001) as shown in Figure 3(b), and the mean of level of the adduct HεdC in RA patients was approximately five times higher than that in controls. Moreover, in order to match the number of sex between RA patients and controls, the datum of 14 women and 7 men were randomly selected, and it was confirmed that HεdC (but not 8-oxo-dG and εdA) levels were significantly higher in RA patients than those in controls (P < 0.0001, data not shown).

Bottom Line: Results.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.

View Article: PubMed Central - PubMed

Affiliation: Department of Respiratory Medicine, Allergy and Rheumatic Diseases, Osaka University Graduate School of Medicine, 2-2 Yamada-Oka, Suita, Osaka 565-0871, Japan.

ABSTRACT
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.

No MeSH data available.


Related in: MedlinePlus