RA is a common autoimmune heterogeneous joint disease of still unknown etiology. One of the characteristic features of RA is oxidative stress, most probably induced and stimulated by inappropriate B and T-cell activity. We have hypothesized, that oxidative stress together with impaired DNA damage response to oxidative DNA lesions could be responsible for increased incidence in RA patients of some diseases with genetic instability background such as lymphoma.

Material and methods:
We determined the level of oxidative DNA lesions and the kinetics of removal of DNA damage induced by TBH in PBMCs of 30 RA patients and 30 healthy individuals. The metrics from DNA repair study were correlated with genotypes of common polymorphisms of key BER genes as well as their expression levels. DNA repair were evaluated by comet assay, the genotypes of the polymorphism were determined by Taqman Assay and PrimeTime qPCR Assay was used to analyze the expression profile of genes related to BER.

We observed an association between RA occurrences and impaired DNA repair in PBMCs. After dividing the subjects by controls’ quartiles of DNA repair efficiency, we found an association between an increased risk of RA and inefficient DNA Repair. We also identified interaction between inefficient DNA Repair and polymorphism of the UNG gene (rs246079), and lower expression of key BER genes – MUTH, NEIL3 and UNG.

Our result suggest that the genetic variations within BER genes as well as epigenetic factors may be linked with RA by the modulation of the cellular response to oxidative stress.

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