| Background Systemic lupus erythematosus(SLE)is a common autoimmune disease,and genetic factors may play an important role in the disease.Glucocorticoids(GCs)are the main drugs for the treatment of SLE.GCs play a pharmacological role through binding with glucocorticoid receptor,however,it is not clear whether the mutation of the GR gene in SLE patients and whether the mutation affects the occurrence and clinical manifestations of SLE is not clear.Objectives To identify the association of glucocorticoid receptor(GR)genetic variations with systemic lupus erythematosus(SLE).Methods A case-control study was carried out,400 cases and 400 controls were collected from the First Affiliated Hospital of Medical University Of Anhui and the Second Affiliated Hospital of Medical University Of Anhui,which was used to analyze the relationship between SLE pathogenesis and single nucleotide polymorphism;430cases and 430 controls were collected from the First Affiliated Hospital of Medical University Of Anhui and the Second Affiliated Hospital of Medical University Of Anhui,which was used to analyze the incidence and base for lupus relationships between copy number variations,which overlaps the number of cases in 650 cases,to analyze the interaction of single nucleotide polymorphisms and gene copy number variation.Collection of general demographic data and related clinical data by self designed adjustment questionnaire,peripheral blood 3-5ml of SLE patients and normal controls were used for SNPs typing.DNA extraction kit DNA,extraction of DNA is placed in the refrigerator at-80?.DNA was extracted using genomic DNA extraction kit,and tag single nucleotide polymorphisms(SNPs)were identified by Haploview(4.0)Project from the Chinese Hap Map Project.Besides,eighteen tag SNPs of GR gene were genotyped by the Multiplex SNa Pshot technique.The Accu Copy TM multigene copy number detection technique was used to detect the CNV typing.Results1.Two GR gene SNPs were associated with the pathogenesis of SLE:rs6865292(dominant model: crude OR=1.526,95%CI:1.151-2.025,P=0.003;adjusted OR=1.525,95%CI:1.149-2.023,P=0.004;PBH=0.036)and rs9324921(dominant model:crude OR=1.556,95%CI:1.173-2.062,P=0.002;adjusted OR=1.553,95%CI:1.171-2.060,P=0.002;PBH=0.036).2.The haplotype analysis of GR gene SNPs manifested that the haplotype of “CCGGG”(OR=2.701,95%CI:1.348-5.410,P=0.004;PBH=0.036)was a risk factor for the development of SLE.3.A lower frequency of A-allele of SNP rs4607376(P =0.021;OR=0.794,95%CI:0.652-0.966,PBH=0.126),higher frequency of C-allele of SNP rs6865292(P=0.019,OR=1.317,PBH=0.126)and A-allele of SNP rs9324921(P =0.019,OR=1.317,PBH=0.126)may be risk factors for developing SLE.4.The rs7719514(recessive model: crude P=0.044;adjusted P=0.044,PBH=0.264),rs7701443(recessive model: crude P=0.044,adjusted P=0.045;PBH=0.264),rs4607376(recessive model: crude P =0.027;adjusted P=0.026;PBH=0.264)and haplotype “CAGCG”(P=0.044;PBH=0.198)showed marginal association with the pathogenesis of SLE.5.In case group,there were no significant differences between non-lupus nephritis and lupus nephritis.The SNP rs12054797(F=3.228,P=0.041,PBH=0.342),rs2963156(F=3.163,P=0.043,PBH=0.342)might be marginal associated with disease activity.6.The copy number variation(CNV)was a risk factor for developing SLE(crude OR=6.218,95%CI:1.818-21.269,P =0.004;adjusted OR=6.237,95%CI:1.816-21.420,P=0.004).Conclusions There are differences in GR gene between SLE patients and normal controls.SNP rs6865292,SNPrs9324921,GR gene haplotypes”CCGGG” and GR gene copy number variation are risk factors for the pathogenesis of SLE.GR genetic variation may play an important role in the pathogenesis of SLE. |
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