| BackgroundSystemic lupus erythematosus(SLE)is a severe,chronic autoimmune disease that affects multisystem.The immune system attacks the healthy tissues and cells because of the loss of immunological tolerance to self-antigens in autoimmunity.Therefore,SLE is characterized by a multitude of autoantibody production,immune complex deposition and systemic inflammation.The etiology and pathogenesis of SLE are complex and still not fully elucidated even though people have put much energy into studying the SLE.Fortunately,amounts of studies has shown that SLE associated with hormone,environmental,and genetic factors,and heredity plays a vital role.Previous studies have focused on the correlation between encoding RNA and disease,in recent years,long noncoding RNAs(lncRNAs)come to be the focus of research.Members of lncRNAs have been reported in diverse gene-regulatory mechanisms such as chromatin remodeling,gene transcription,RNA splicing,and protein transport.Besides,lncRNAs are involved in regulating the development and differentiation of T cells,B cells and NK cells.Recently,studies have validated that lncRNAs were indeed involved in the development of cancer,cardiovascular disease and various autoimmune diseases,such as lncRNAC5T1 may participate in the development of rheumatoid arthritis.With the in-depth study of lncRNA,the results reveal that lncRNAs may play a vital role in the development of autoimmune diseases.Based on previous study of lncRNAs in our group,we refer that lncRNAs might be involved in the onset of SLE and may be new therapeutic targets.ObjectiveTo detect the expression levels of five lncRNAs(lnc0640,lnc3643,lnc5150,lnc7514and lncagf)in the peripheral blood mononuclear cells(PBMCs)of patients with SLE,the correlation between expression levels and clinical or laboratory features and the relationship between the sinle-nucleotide polymorphisms(SNPs)of lncRNAs(lnc0640,lnc5150)and SLE in a Chinese Han population.MethodsA two phases case-control study design were applied.In the first stage,76 SLE patients and 71 healthy controls were enrolled,PBMCs were obtained from the blood samples of all subjects.Expression levels of lncRNAs were detected by quantitative real-time reverse transcription polymerase chain reaction(qRT-PCR),their associations with clinical and laboratory characteristics were analyzed.In the second stage,we examined660 SLE patients and 860 healthy controls(HC).Four lnc0640 SNPs(rs8121205,rs6085190,rs6085189,rs13039216)and two lnc5150 SNPs(rs144047453,rs141561256)were genotyped using TaqMan genotyping assays on Fluidigm 192.24 system.The distribution of genotype and allele frequencies of all SNPs were detected,the genotype effects of dominant and recessive models were also analysed.The association between SNPs and clinical manifestations in SLE patients were analysed.The results of this study were analyzed by SPSS 23.0,andα=0.0083(0.05/6)when the statistical analysis of genotype frequencies needed to perform the Bonferroni multiple correction,αwas0.05 in the other analysis.Results(1)Compared with healthy controls,the expression levels of lnc0640 were significantly overexpressed in SLE patients while the expression levels of lnc5150 were significantly decreased(Z=-2.233,P=0.026;Z=-6.016,P<0.001,respectively);Lnc3643,lnc7514and lncagf showed no significant difference in expression levels between SLE patients and the healthy control(all P>0 0.05);No significant differences in expression levels of lnc0640,ln5150,lnc7514 and lncagf between LN and non-LN(all P>0 0.05)were observed.(2)Further analysis in patients with SLE showed the expression levels of lnc3643 was significantly decreased in LN compared with SLE patients without nephritis(Z=-2.441,P=0.015),and the expression levels of lnc3643 and lnc7514 were correlated with disease activity,C-reactive protein(CRP)(all P<0.05)and erythrocyte sedimentation rate(ESR)(all P<0.05).(3)No significant differences were detected for the distribution of allele and genotype,we failed to find any significant results about dominant and recessive models of all SNPs.(4)Further analysis in SLE patients revealed that the AA genotypes and A allele of the lnc5150 rs141561256 polymorphism were significantly higher in SLE patients with LN(χ~2=8.783,P=0.012;χ~2=6.478,P=0.02;respectively).Moreover,the genotype and allele distribution of the lnc0640 rs13039216 were also associated with discoid lupus and photosensitivity in patients with SLE(χ~2=15.521,P<0.001,χ~2=9.991,P=0.002;χ~2=6.612,P=0.037,χ~2=5.515,P=0.019;respectively).ConclusionsCompared to the healthy control,the expression of lnc0640 was over-expressed and lnc5150 expression level was decreased.Further analysis in SLE reveals that the lnc3643 expression with LN is lower than without LN,and lnc3643 expression is negatively correlated with SLEDAI.Genotyping results showed that six SNPs were unrelated to disease susceptibility,whereas,lnc5150 rs141561256 and lnc0640rs13039216 may be associated with the occurrence of certain clinical symptoms of SLE. |
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