XRCC1Arg399Gln and Arg194Trp Polymorphisms and Risk of Systemic Lupus Erythematosus in an Iranian Population: A Pilot Study

Abstract

Background. Evidences are suggesting that DNA damage is implicated in development of systemic lupus erythematosus (SLE). Therefore we focused on two common XRCC1 polymorphisms (Arg399Gln and Arg194Trp) in SLE susceptibility in South East of Iran. Methods. Peripheral blood DNA was extracted from 163 SLE patients and 180 healthy controls. PCR-restriction fragment length polymorphism method was used for genotyping of XRCC1 Arg399Gln and Arg194Trp polymorphisms. Results. The frequency of Arg/Gln genotype of the XRCC1 Arg399Gln polymorphism was significantly lower in SLE patients than controls. Moreover, lower frequency of Arg/Gln genotype was found in SLE patients with malar rash compared to patients without this manifestation. No association was observed between XRCC1 Arg194Trp polymorphism and increased risk of SLE in studied population. Haplotype analysis revealed no correlation between four haplotypes of XRCC1 Arg399Gln and Arg194Trp polymorphisms and SLE risk. Conclusion. These findings suggest that XRCC1 399 Arg/Gln heterozygous genotype plays a protective role in SLE susceptibility.

Association Between Functional Polymorphisms of DNA Double-Strand Breaks in Repair GenesXRCC5,XRCC6andXRCC7with the Risk of Systemic Lupus Erythematosus in South East Iran

“…Moreover, viral infections, drugs, chemicals, and exposure to ultraviolet (UV) radiation are also considered as potential environmental factors of SLE (Parks et al, 2005;Doria et al, 2008). Family and genetic studies, for example, monozygotic and dizygotic twins, indicate that genetic predisposition contributes to the development of SLE; therefore, numerous studies identified the relationship between different genetic variants and SLE susceptibility (Aringer and Hiepe, 2011;Bahrehmand et al, 2012;Nakou et al, 2013;Salimi et al, 2014). Furthermore, excessive DNA damage in SLE patients, besides the accumulation of nucleoproteins, may produce immunogenic antigens, which lead to the production of self-reactive antibodies (Abs).…”

“…DNA repair genes can contribute to SLE predisposition (Herrick et al, 1995), and polymorphisms of XRCC1, XRCC3, and XRCC4 genes are associated with manifestation of SLE Lin et al, 2009;Warchol et al, 2012;Salimi et al, 2014). Moreover, there are numerous variants in XRCC5, XRCC6, and XRCC7 genes, which have been associated with different diseases, such as gastric cancer (Lim et al, 2002), head and neck cancer (Chang et al, 2006), breast cancer (Fu et al, 2003), glioma (Wang et al, 2004), and AML (Wang et al, 2009).…”

Possible Association Between XRCC1 Genes Polymorphisms and Systemic Lupus Erythematosus

“…Previous studies have shown that genetic factors play a key role in this disease (2)(3)(4)(5). Anti-genicity could be increased by reactive oxygen species (ROS), which causes DNA conformation changes and DNA base damages or breaks (6). DNA repair enzymes monitor the DNA structure to correct damaged nucleotide produced by methylation, oxidation or oxidative damage; therefore, DNA repair mechanisms have an essential role in genome stability (7).…”

“…Other investigations by Lin et al and Warchol et al showed that Arg/Arg genotype of rs25487 had a protective role against SLE in Chinese and Polish populations (8,11). In the Iranian population, only one investigation was done, in which Salimi et al showed that Arg/Gln had a protective role against SLE (6). Another SNP (rs1799782) was explored in 2 studies, which showed no association between the related SNP and SLE susceptibility (6,11).…”

“…In the Iranian population, only one investigation was done, in which Salimi et al showed that Arg/Gln had a protective role against SLE (6). Another SNP (rs1799782) was explored in 2 studies, which showed no association between the related SNP and SLE susceptibility (6,11). The effect of rs25489 on SLE has not been investigated and the result of another SNP, which has been investigated should be elucidated.…”