DNA Repair Gene XRCC1 And MUTYH Polymorphisms And Risk Of Systemic Lupus Erythematosus In The Han Chinese Population

Objective: Systemic lupus erythematosus(SLE)is the prototype of the systemic autoimmune diseases characterized by protean clinical manifestations affecting almost any organ of our body.So far,the pathogenesis of SLE has not yet been fully elucidated.Genetic studies have demonstrated a strong contribution of DNA repair gene variants to SLE incidence and the clinical manifestations of SLE.Single nucleotide polymorphisms(SNPs)lead to differences in gene expression and function.X-ray repair cross-complementing gene 1(XRCC1)and(MUTYH)gene are the major DNA repair genes ofbase excision repair pathway(BER).Their proteins repair the damaged DNA caused by a variety of materials.They play an important role to maintain the individual’s genetic stability.Their gentic polymorphisms are associated with various diseases.This study was to investigate the associations of XRCC1(rs25487)and MUTYH(rs3219463)gene SNP and SLE susceptibility,clinical manifestation and autoantibodies of SLE patients.Methods : Case-control design was applied in this study.The case group include of 172 SLE patients in Chinese Han population.Control group consist of 172 healthy patients from Center of Health Examination.All the patients were from the Affiliated Hospital of Southwest Medical University during the same study period.All the control subjects were frequency-matched to the cases on gender and nationality.The detailed information on each patient was investigated including the demographic information and Clinical and laboratory datas.The genomic DNA was extracted from all peripheral blood samples.The locus of XRCC1 gene rs25487 and MUTYH gene rs3219463 were genotyped by polymerase chain reaction restriction fragment length polymorphism(PCR-RFLP)method.Then,the chi-square(x2)test was used to analysis the genotype and allele frequency of Hardy Weinberg equilibrium.And unconditioned Logistic regression analysis was used to estimate the odds ratio(OR)corresponding to 95% confidence interval(CI),line of single nucleotide polymorphisms associated with SLE risk、Clinical and laboratory feature analysis,threshold of statistical significance is P values<0.05.Statistical analysis was performed by SPSS 19 software.Results: Genotype and allele frequeneies of XRCC1(rs25487)and MUTYH(rs3219463)were signifieantly different between the SLE cases and health controls(P<0.05).XRCC1(rs25487)gene to the wild genotype GG as the reference,carrying AA OR GA+AA patientswere increased relative risk of SLE(OR values were 2.420,1.576;95%CI values were(1.012-5.786),(1.024-2.426);Pvalues were 0.047,0.038).XRCC1(rs25487)gene to the wild allelic genes G as the reference,carrying mutant allele A patientswere increased relative risk of SLE(OR values was 1.448;95%CI values was(1.052-1.995);Pvalues was 0.023).Nervous system damage ratio is higher in rs25487 AA genotype SLE patients than the others(P=0.029).Anti-histone antibody positive rate is increase in rs25487 GA genptype SLE patients than the others(P=0.030).MUTYH(rs3219463)gene to the wild genotype AA as the reference,carrying GG OR GA+GG patientswere increased relative risk of SLE(OR values was 2.478;95%CI values was(1.139-5.393);P values was 0.022).MUTYH(rs3219463)gene to the wild allelic genes A as the reference,carrying mutant allele G patientswere increased relative risk of SLE(OR values was1.427;95%CI values was(10.43-1.952);P values was 0.026.Skin lesions ratio is higher in rs3219463 GG genotype SLE patients than the others(P=0.029).Conclusion: the XRCC1(rs25487)polymorphismincrease the susceptibility to SLE and associated withthe presence of neuropsychiatric manifestations and anti-histone antibody.The concomitance of DNA repairpolymorphic site,MUTYH(rs3219463),was associated with SLE susceptibility and the presence of skin lesions.Taken together,thepolymorphic sites of DNA repair gene XRCC1 and MUTYH may predisposeto the development of SLE and particular clinical and laboratory features.This study revealed that the polymorphisms of XRCC1(rs25487)and MUTYH(rs3219463)might decrease the DNA repair ability andincrease the susceptibility to SLE.