Gene Polymorphism of XRCC1 in Systemic Lupus Erythematous

Introduction: There are debates about the role of the X-ray repair cross-complementation group 1 (XRCC1) Arg399Gln gene in the pathogenesis of Systemic Lupus Erythematosus (SLE). Methods: The study was a case-control study carried out on 100 recently diagnosed SLE patients compared to 100 control subjects. The study of XRCC1 Arg399Gln polymorphism was performed by a polymerase chain reaction and restriction fragment length polymorphism. Results and Discussion: A higher frequency of ‘G’ allele in SLE (38.5%) versus control (32%) was noticed; however, this difference was not statistically significant (p = 0.174). Besides, a slightly higher frequency of G/G genotype was found in SLE (22%) vs. control (12%); again, this difference was not statistically significant (p = 0.157). A statistically significantly higher proportion of arthritis, serositis, and thrombocytopenia was observed in the A/A genotype (p = 0.010, 0.032, and 0.036, respectively). Furthermore, we noticed a statistically significant lower hemoglobin level in G/G genotype (p = 0.027). Otherwise, there was no statistically significant difference between the three genotypes regarding other parameters: photosensitivity, malar rash, oral ulceration, ANA, anti-dsDNA antibody, anemia, leucopenia, neurologic manifestations, and all lab parameters except hemoglobin level. Similar results were reported previously. According to genotype, in the study of Clinical and laboratory parameters in SLE patients, a statistically significantly higher proportion of arthritis, serositis, and thrombocytopenia was observed in the A/A genotype (p =0 .01, 0.032, and 0.036 respectively). Furthermore, we noticed a statistically significant lower hemoglobin level in G/G genotype (p = 0.027). These findings suggest a pathogenic connection between the seriousness of the defective DNA repair and the autoimmune severity; such connection is consistent with that found in several murine models. Additionally, negative regulation of the genes encoding the proteins involved in the NER pathway in SLE patients, specifically and XPC, has been found previously. Conclusion: The present study highlights the higher insignificant increase of G allele and GG genotype of XRCC1 399 gene in patients with SLE compared to healthy control. This increase was significantly associated with anemia in patients, which may reflect the aggravation of environmental risk factors to SLE associated with the reduced repair of DNA. Further longitudinal studies are required to validate the present findings.

The Association Between the XRCC1 Arg399Gln Polymorphism and the Risk of Head and Neck Cancer: An Updated Meta-Analysis Including 14586 Subjects

Background: Accumulated evidence shows that DNA repair gene X-ray repair cross complementing group 1 (XRCC1) may determine individual susceptibility to head and neck cancer (HNC) as a major DNA repair gene. However, the results from previous studies have been conflictive and inconsistent. In order to more accurately estimate and integrate the association between XRCC1 Arg399Gln polymorphism and HNC risk, we conducted a meta-analysis including 14586 subjects. Methods: In this meta-analysis, literatures were collected up until September 15, 2020 through multifarious retrieval strategies by searching through electronic databases of PubMed, Cochrane Library, EMBASE, Medline, Web of Science and CNKI. The association between the XRCC1 Arg399Gln polymorphism and HNC was analyzed through calculating summary odds ratios (OR) and 95% confidence intervals (CI). Results: Thirty-one studies consisting of 6025 cases and 8561 controls were identified and analyzed. No significant association between XRCC1 Arg399Gln polymorphisms and HNC risk was found under the allelic (OR = 0.94, 95% CI: 0.82-1.07, P = 0.35), homozygous (OR = 0.99, 95% CI: 0.81-1.21, P = 0.91), heterozygous (OR = 1.01, 95% CI: 0.90-1.13, P = 0.91), dominant (OR = 1.05, 95% CI: 0.85-1.29, P = 0.67) or recessive (OR = 0.93, 95% CI: 0.80-1.08, P = 0.35) genetic models in the overall comparison. In addition, subgroup analyses according to tumor site also displayed no significant association between XRCC1 Arg399Gln polymorphisms and HNC risk. However, subgroup analyses based on ethnicity indicated that HNC risk was significantly related to Arg399Gln genetic heterozygous model (OR = 1.21, 95%CI: 1.04-1.42, P = 0.02) and dominant model (OR = 1.27, 95%CI: 1.02-1.60, P = 0.04) in Caucasians populations. Conclusion: The results from this meta-analysis suggest that the XRCC1 Arg399Gln variants (Arg/Gln and Arg/Arg+Arg/Gln) may contribute to high HNC risk among Caucasians. Further well-designed studies and larger sample sizes are needed to validate our findings.

Evaluation of the ERCC2 (Lys751Gln), MSH2 (gIVS12-6TC), RAD54 (Ala730Ala), XPC (Lys939Gln), XPG (Asp1104Hist), XRCC1 (Arg399Gln) and XRCC3 (Thr241Met) gene polymorphisms in the Ecuadorian population with retinoblastoma

Background Retinoblastoma is a neoplasia that starts in the retina and may have inheritable or sporadic genetic predisposition. This affects children, mainly those who are under 5 years old. Approximately 9,000 new cases are diagnosed per year worldwide. In Ecuador this disease has an incidence of 1 per each 20,000 live births. The genetic predisposition to develop retinoblastoma is strongly influenced by RB1 gene, and may be influenced by the presence of genetic polymorphisms which intervene in the DNA repair system. Methods This study has analyzed the genotype frequency of ERCC2 (Lys751Gln), MSH2 (gIVS12-6TC), RAD54 (Ala730Ala), XPC (Lys939Gln), XPG (Asp1104Hist), XRCC1 (Arg399Gln), and XRCC3 (Thr241Met) polymorphisms of different repair genes, genotyping 90 individuals affected with retinoblastoma and 80 healthy individuals through polymerase chain reaction / restriction fragments length polymorphism and sequencing analysis. Results The presence of the (C/C) mutant homozygous genotype of XPC (Lys939Gln) polymorphism triggers a significant risk of developing retinoblastoma with an odds ratio (OR) of 3 (CI: 1.22-9.84; p < 0.05). Likewise, the A/G heterozygous genotype and the combination A/G+G/G of XRCC1 (Arg399Gln) polymorphism presented ORs of 9.7 (CI: 4.45-21.08; p < 0.001) and 7.55 (IC: 3.57-16; p < 0.001), respectively. Conclusions The genetic variants XPC (Lys939Gln) and XRCC1 (Arg399Gln) may be associated with the risk of developing retinoblastoma in the Ecuadorian population.