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THU0276 Increased Oxidative DNA Damage and Impaired Gene Repairing Pathway in Patients with Systemic Lupus Erythematosus
  1. S. Donmez1,
  2. G.E. Pamuk2,
  3. O. Doganlar3,
  4. O.N. Pamuk1
  1. 1Rheumatology
  2. 2Hematology
  3. 3Trakya University Medical Faculty, Edirne, Turkey

Abstract

Background Systemic lupus erythematosus (SLE) is a chronic autoimmune disease and may affect multiple organs and systems. Definite etiology and pathogenesis of disease is unknown. Apoptosis, defective clearance of apoptotic materials, uncontrolled DNA damage related to oxidative stress play important roles in the pathogenesis of SLE.

Objectives In this study we aimed to evaluate some parameters related to oxidative stress, apoptosis and gene repairing system in SLE and lupus nephritis (LN) patients.

Methods The study included 10 patients with active SLE, 10 patients with active LN and 10 healthy controls. The demographical and clinical features of patients were obtained from medical charts. RNA isolation from peripheral blood was performed according to protocol of RNA kit. RT-PCR was used to analyze gene expressions of SOD, CAT, glutathione synthetase, survivin, BCL-2, CCN D1 and that of genes in the apoptotic pathway. To compare the features of study groups, one-way ANOVA test was performed and Duncan test was used as posthoc analysis.

Results 8-hydroxy-deoxyguanosine (8-OHdG) which is the most common stable product of oxidative DNA damage caused by ROS is significantly higher in SLE (618±293) and LN groups (732±303) than in healthy controls (333±128) (p values <0.01). In addition, genomic template stability (GTS) in SLE and LN groups were significantly lower than in healthy controls (p values <0.001). Telomer length was used to assess overal biological aging. In our SLE and LN patients, telomer length is shortened than in healthy controls (p values <0.01).

We also evaluated the antioxidant system gene expression. We detected that main antioxidant system gene expression like SOD, SOD2, GS and GPX were significantly decreased in LN patients than in SLE and healthy controls. In the contrary, gene repair pathway related gene expression such as TDG, SMUG1 and RAD18 were significantly increased in SLE and especially in LN groups when compared to healthy controls (p values <0.05).

In LN patients, p53 gene was expressed significantly more than in SLE and controls. This gene was also expressed significantly more in SLE than in controls (p<0.05).

The expression of apoptosis associated genes like BAX, APAF, CYTC, CASPASE3 were elevated in LN than in SLE and healthy controls (p values <0.01). Apoptosis inhibitor genes like survivin, livin, XIAP and BCL2 were expressed signficantly higher in LN patients than in SLE and controls (p values <0.01). These genes were also expressed higher level in SLE patients than in controls (p<0.05).

Conclusions In SLE patients, particularly in LN group, oxidative DNA damage is increased and antioxidant gene expression is decreased. Gene repair pathway is also impaired in SLE and LN. Although, genes related to inhibition of apoptosis is elevated, this elevation is not enough to eliminate the activation of apoptosis.

Disclosure of Interest None declared

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