TY - JOUR T1 - Patients with Systemic Sclerosis Present Increased DNA Damage Differentially Associated with DNA Repair Gene Polymorphisms JF - The Journal of Rheumatology JO - J Rheumatol DO - 10.3899/jrheum.130376 SP - jrheum.130376 AU - Gustavo Martelli Palomino AU - Carmen L. Bassi AU - Isabela J. Wastowski AU - Danilo J. Xavier AU - Yara M. Lucisano-Valim AU - Janaina C.O. Crispim AU - Diane M. Rassi AU - Joao F. Marques-Neto AU - Elza T. Sakamoto-Hojo AU - Philippe Moreau AU - Percival D. Sampaio-Barros AU - Eduardo A. Donadi Y1 - 2014/02/01 UR - http://www.jrheum.org/content/early/2014/01/29/jrheum.130376.abstract N2 - Objective Patients with systemic sclerosis (SSc) exhibit increased toxicity when exposed to genotoxic agents. In our study, we evaluated DNA damage and polymorphic sites in 2 DNA repair genes (XRCC1 Arg399Gln and XRCC4 Ile401Thr) in patients with SSc. Methods A total of 177 patients were studied for DNA repair gene polymorphisms. Fifty-six of them were also evaluated for DNA damage in peripheral blood cells using the comet assay. Results Compared to controls, the patients as a whole or stratified into major clinical variants (limited or diffuse skin involvement), irrespective of the underlying treatment schedule, exhibited increased DNA damage. XRCC1 (rs: 25487) and XRCC4 (rs: 28360135) allele and genotype frequencies observed in patients with SSc were not significantly different from those observed in controls; however, the XRCC1 Arg399Gln allele was associated with increased DNA damage only in healthy controls and the XRCC4 Ile401Thr allele was associated with increased DNA damage in both patients and controls. Further, the XRCC1 Arg399Gln allele was associated with the presence of antinuclear antibody and anticentromere antibody. No association was observed between these DNA repair gene polymorphic sites and clinical features of patients with SSc. Conclusion These results corroborate the presence of genomic instability in SSc peripheral blood cells, as evaluated by increased DNA damage, and show that polymorphic sites of the XRCC1 and XRCC4 DNA repair genes may differentially influence DNA damage and the development of autoantibodies. ER -