Correlation Between Single Nucleotide Polymorphism Of The DNA Repair Gene XRCC1 And Systemic Lupus Erythematosus

Single nucleotide polymorphism(SNP) is defined as single base sequence disparity of genome DNA in certain colonia or normal individuals,which is the simplist and most extensive polymorphic type in genome of biosystem.Over 90%of the essential qualities reflection on genetic information of human gene polymorphism was due to SNP characterized as extensive distribution,large quantity and relative stability.The occurrence of SNP may lead to the change of protein sequence or conformation and SNP is considered to be critical to human body constitution resulting in individual variation in liability to certain disease and reaction to certain treatment.Nowadays,researcheres are making great efforts in the exploration of the background of human disease-associated genes,SNP become a hot spot due to its advantages in heredity research.Systemic lupus erythematosus(SLE) is a chronic autoimmune disease characterized by the production of diverse autoantibodies, resulting in immune complex deposition and tissue and organ damage. From the perspective of immunology,SLE is the autoirnrnune response, against the many self-antigens,mainly nuelear antigens such as DNA, Protein and nuclear bodies and so on.DNA has been considered to be one of the most important.DNA repair system continuously monitor chromosome to protect the integrity of DNA.The single nucleotide polymorphisms of DNA repair genes have unconservative amino acid replacements,of which the mutants can change the function of protein, repair capability.The DNA repair capability of individual is close to the polymorphic genotypes.The defect of DNA repair capability is connected with the function deletion of DNA repair protein resulting from gene mutations,mostly with the different repair capability from genetic polymorphisms.The X-ray repair cross-complementing 1(XRCC1) plays a critical role in repair of single-strand breaks and base damage,and is located on human chromosome 19q13.2-13.3.In encoding area,single nucleotide polymorphism results in the corresponding change of amino acid.A case-control study was conducted to test the allele frequencies and genotype frequencies of XRCC1 Arg194Trp,Arg399Gln and Arg399Gln by AS-PCR,from which risk genotypes can be found.It can be helpful to analyze possible mechanism of systemic lupus erythematosus and their roles to discuss the association between the risk genotypes and systemic lupus erythematosus and the interaction between genotypes and clinical or laboratory feature,which can be used in studying the etiology of systemic lupus erythematosus.The relations between genotypes and clinical or laboratory feature,will provide an evidence for individual gene diagnosis.Objective:To explore frequencies and single nucleotide polymorphisms distribution of XRCC1 gene,and analysis the susceptibility to systemic lupus erythematosus in Chinese Han population and the interaction between genotypes and clinical or laboratory feature.Methods:allele specific polymerase chain reaction(AS-PCR)was used to comparatively study the SNP in XRCC1 Arg194Trp,Arg399Gln and Arg399Gln in 39 patients with SLE and 40 randomly selected,unrelated healthy controls of Chinese Han population. Results:(1)Genotype and allele frequeneies of XRCC1 Arg399Gln were signifieantly different between the SLE cases and controls(P＜0.05), Arg399GInGA+AA was associate with the inereased risk of SLE [OR=3.92;95%CI(1.51-10.18)];(2) Hematological system damage ratio is lower in Arg194Trp CT+TT genotype SLE patients than the others. Anti SS-A antibody positive rate is increase in Arg194Trp CT+TT genptype SLE patients than the other.Conclusion:Genotype and allele frequeneies of XRCC1 Arg399Gln polymorphism and the incidence of SLE have some relevance.The genotype Arg399Gln GA+AA possiblely is the susceptible gene of SLE. It is related between the SNP in XRCC1 Arg194Trp and autoantibody Production,hematological system damage in SLE Patients.