Patients with systemic sclerosis present increased DNA damage differentially associated with DNA repair gene polymorphisms.
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.


CONCLUSIONS
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.
From the Program of Basic and Applied Immunology, Faculdade de Medicina de Ribeirão Preto, University of São Paulo (FMRP-USP); Department of Basic Sciences in Health, Faculty of Medical Sciences, Federal University of Mato Grosso (UFMT); Department of Genetics, FMRP-USP; Department of Physics and Chemistry, Faculty of Pharmaceutical Sciences of Ribeirão Preto (FCFRP-USP); Department of Clinical and Toxicological Analyses, Faculty of Pharmaceutical Sciences, University Federal Rio Grande do Norte State (UFRN); Department of Medicine, FMRP-USP; Unit of Rheumatology, Department of Internal Medicine, Faculty of Medical Sciences, State University of Campinas, (UNICAMP), Brazil; Commissariat à l'Energie Atomique et aux Energies Alternatives, Institut des Maladies Emergentes et des Therapies Innovantes, Service de Recherches en Hemato-Immunologies, Hôpital Saint-Louis, Paris, France; Division of Rheumatology, Faculdade de Medicina, Universidade de São Paulo (FM-USP), São Paulo, Brazil.
Gustavo Martelli
GM
Palomino
Carmen L
CL
Bassi
Isabela J
IJ
Wastowski
Danilo J
DJ
Xavier
Yara M
YM
Lucisano-Valim
Janaina C O
JC
Crispim
Diane M
DM
Rassi
Joao F
JF
Marques-Neto
Elza T
ET
Sakamoto-Hojo
Philippe
P
Moreau
Percival D
PD
Sampaio-Barros
Eduardo A
EA
Donadi
D000328:Adult; D000483:Alleles; D004249:DNA Damage; D004260:DNA Repair; D004268:DNA-Binding Proteins / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D042822:Genomic Instability; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D012595:Scleroderma, Systemic / Q000235:genetics*; D000076105:X-ray Repair Cross Complementing Protein 1
D004268:DNA-Binding Proteins; D000076105:X-ray Repair Cross Complementing Protein 1; C000619371:XRCC1 protein, human; C101467:XRCC4 protein, human
COMET ASSAY; DNA DAMAGE; DNA REPAIR; SYSTEMIC SCLEROSIS; XRCC1 AND XRCC4