Association Between Functional Polymorphisms of DNA Double-Strand Breaks in Repair Genes XRCC5, XRCC6 and XRCC7 with the Risk of Systemic Lupus Erythematosus in South East Iran

DNA repair is reduced in patients suffering from systemic lupus erythematosus (SLE), and it can induce the production of autoreactive antibodies due to the accumulation of DNA damage and nucleoprotein that produce immunogenic antigens. The accumulations of anti-Ku and DNA-PKcs antibodies, which are involved in nonhomologous DNA end joining pathway, have been detected in SLE patients. The present study was designed to evaluate the association of XRCC5, XRCC6, and XRCC7 polymorphisms with SLE susceptibility. Polymerase chain reaction (PCR) was performed to genotype 163 SLE patients and 180 healthy controls for the XRCC5 variable number of tandem repeat (VNTR) polymorphism. The genotype analysis of XRCC6-61C>G and XRCC7 6721G>T polymorphisms was performed using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) technique. There was a significant association between XRCC5 VNTR, XRCC7 6721G>T polymorphisms and risk of SLE development. Notably, the frequency of XRCC5 VNTR 0R allele and genotypes with 2R allele was greatly enhanced in SLE patients with Malar rash (p=0.032 and p=0.024, respectively). Moreover, a higher frequency of genotypes with the XRCC5 VNTR 2R allele was observed in SLE patients with a positive antinuclear antibody (ANA) test (p=0.03). The present study shows an association between the XRCC5 VNTR, XRCC7 6721G>T polymorphisms and SLE. These polymorphisms might be genetic risk factors for SLE susceptibility and some SLE manifestations in the population southeast of Iran.