Association Of TLR7Gene Copy Number Variations And Systemic Lupus Erythematosus In Chinese Han Populations

Backgroud and ObjectiveSystemic lupus erythematosus is a performance for a variety of autoantibodies generated, immune complex deposition, leading to damage of multiple organ autoimmune disease. SLE pathogenesis is not very clear, most scholars believe that the mutual interaction caused by heredity, infection, sex hormones, environmental factors such immune regulation disorder lead to autoimmune diseases. The incidence and prevalence rate of different races and regions have a lot of differences, the SLE patients clinical phenotype of different regions and ethnic have differences also, Asian populations are more common renal involvement than European popμlations. Suggesting that genetic factors play a role in the pathogenesis of SLE and clinical phenotype complexity. SLE familial aggregation phenomenon is an important evidence of the genetic factors involved in, about11%-12%of the first-degree relatives of patients with systemic lupus erythematosus. Pedigree twin study also suggest that the prevalence of monozygotic ratio (24%-65%) is higher than the proportion of fraternal twins (2%-9%), the the wins risk of8-29times the normal.With the progress in genetics, research method updates, scholars use a genome-wide association analysis of single nucleotide polymorphism (SNP-GAWS) method to study SLE pedigrees, found some valuable susceptibility genes. SNP-GWAS people can explain a relatively small part of the risk of disease, unlike SNP, gene copy number variation not only the genetic diversity of a major performance, but also an important genetic basis of human genetic variation. With the completion of the Human Genome Project, we found many SLE susceptibility genes and loci, shen et al studied genetic polymorphism of TLR7area in4334cases of lupus patients and4940controls of Asian populations,demonstreded TLR7SNP (rs3853839) associated with SLE susceptibility. Another study showes the same correlation of the ETS1、WDFY4、TNIP1and PRDM1gene polymorphism with SLE susceptibility. FCGR3B, C4, CCL3L1gene copy number variation found correlation with SLE. Gene copy number variation and other autoimmune diseases have been studied extensively. It has been found that the the gene CNVs phenomenon that can increase susceptibility of human autoimmune diseases.TLR7is a kind of Toll-like receptor family. Main ecognize viral single-stranded RNA, as well as identification the synthetic antiviral molecules, such as Imiquimod, R848, Loxoribine. Promote inflammation reaction through MyD88signaling pathway, mediated non-specific innate immune response. TLR7gene located on the short arm of the X chromosome2District2zone, animal model studies have shown that the occurrence of of TLR7overexpression induced murine lupus, lack a TLR7of MRL mice showed antinuclear antibody reduce, glomerular showed low levels of immune complexes deposition. In addition, the TLR7gene copy number was4-23times in transgenic mice, the expression of TLR7mRNA substantial increase, and resulting in a severe inflammatory response. Xu Wei et al study found TLR7mRNA significantly higher in SLE patients with active, prompt of TLR7and SLE activity related. TLR7abnormalities expression may be related to the lupus patients’pathological process of arthritis.At home and abroad about the study of TLR7gene and SLE or SLE-LN focuses on the SNP. With the completion of the gene copy number variation map, gene copy number was gradually paid attentioned. Part of the gene copy number variation with systemic lupus erythematosus has been studied, lv yong mei in the Chinese Han population study found that C4gene copy number variation is associated with SLE susceptibility of Chinese Han popμlation, total C4gene copy number was not found a correlations with clinical phenotype, and C4A may be closely related to the occurrence of arthritis. Mariam Molokhiaand others found that the distribution of FCGR3B gene copy number (0or1) in African populations and Europeans have differences, prompted SLE low copy number FCGR3B is the risk factors.Apaper Reported TLR7gene copy number variation in systemic lupus erythematosus and healthy controls has no significant difference, TLR7CNVs also no significant relationship with the production of antibodies in lupus patients. Humberto et al reported elevated TLR7GCN for Mexican children SLE is risk factors, confirmed that the number of X-linked genes associated with SLE susceptibility. But there is no significant relationship between the incidence of lupus nephritis and the TLR7GCN.At present, TLR7gene copy number variation with systemic lupus erythematosus and its clinical phenotype correlation has not been reported in the Asian population. Based on the above analysis, the research group intends to measured TLR7gene copy number of Chinese Han337patients with SLE and338healthy controls to investigate the relationship between the Chinese crowd TLR7gene copy number variation with SLE genetic susceptibility, analysis TLR7gene copy number variation relationship between SLE different clinical phenotypes, to provide strong support for exploring SLE genetic susceptibility, and thus provide the basis for the overall understanding of the pathogenesis of SLE genetics.Methods1. In2010-2012, from the nephropathy and rheumatology outpatients and wards of First Affiliated Hospital of Zhengzhou University, to collect blood samples of337patients with SLE. Collected blood samples of338healthy controls from the department of physical examination and Zhengzhou University, Extracting the DNA of blood samples of SLE patients and healthy controls, put in a-80℃refrigerator.2AccuCopyTM technology of multi-gene copy number was used to determine the TLR7gene copy number in337cases of Han Chinese SLE patients and338healthy controls.3. We used cases-control and case-case study to analysis the TLR7gene copy number differences between healthy and SLE patients; According to the clinical phenotype, SLE patients was divided into nephritis group and non-nephritis group; blood system involvement group and non-blood system involvement group; anti-Sm antibody positive group and negative group, analysis TLR7gene copy number and clinical phenotype correlation.4. Apply SPSS17.0statistical software, describe the quantitative data using the median and quartiles, nonparametric rank sum test was used to compare the mean of two independent samples, qualitative data with rate, P＜0.05, statistically significance.Results1. The distribution of TLR7gene copy number in the Chinese Han population:337cases of SLE patients, female SLE group TLR7gene copy number range of1-3,1copy4cases,2copies of the302cases,3copy1case; Male SLE group TLR7gene copy number range1-2,29cases1copy,2copies1case;338cases of healthy controls, the female controls TLR7gene copy number range1-2,1copy of22cases,237cases of2copies. Male,79cases of control group1copy.2. Female group TLR7gene copy number distribution was no significant difference between the SLE patients and healthy control group (Z=-1.175, P=0.240); the male group TLR7gene copy number distribution was no statistically significant difference between the SLE patients and healthy controls (Z=-1.085, P=0.278).3. Female group distribution of TLR7gene copy number between the lupus nephritis group and non-lupus nephritis group was no significant difference (Z=-0.888, P=0.375); the male group TLR7gene copy number distribution between the lupus nephritis group and non-lupus nephritis groups was no significant difference (Z=-0.460, P=0.646).4. Female group TLR7gene copy number distribution between the lupus blood system involvement and non-blood system involvement group was no significant difference (Z=-1.085,P=0.278), male group TLR7gene copy number distribution between between lupus blood system involvement and non-blood system involvement group has no significant difference(Z=-0.340,P=0.733).5. Female group TLR7gene copy number distribution was no significant difference between the positive and negative groups of anti-Sm antibody (Z=-0.529, P=0.597).Male group TLR7gene copy number distribution was no significant difference between the positive and negative groups of anti-Sm antibody (Z=-0.158, P=0.874).Conclusions1. The distribution of TLR7gene copy number in the Chinese Han population: TLR7gene copy number of female SLE group median (P25-P75) was2.00(0.11), and the healthy control group was2.01(0.13).The male SLE group TLR7gene copy number median (P25-P75)0.98(0.08), and healthy control group was0.98(0.05).2. TLR7gene copy number variation has nothing to do with the onset of the Chinese Han SLE patients.3. TLR7gene copy number variation has nothing to do with the clinical pheno-type (renal involvement, blood system involvement, anti-Sm antibody) of Chinese Han SLE patients...