Association Study Of Single Nucleotide Polymorphisms, MRNA Expression Of SOCS1with Systemic Lupus Erythematosus

Background Systemic lupus erythematosus (SLE) is a prototypic autoimmune disease,characterized by autoantibody production, immune complex formation, and subsequentmultiple organ damage. Environmental initiating elements, genetic background andimmune function abnormalities, play crucial roles in the pathogenesis of SLE. As cellsignaling molecules, cytokines have an important effect on the regulation of the immuneresponse, immune cell differentiation and development and inflammatory response.Janus protein tyrosine kinase (JAK) signal transducer and activator of transcription(STAT) signaling pathway plays a leading role in cytokine signaling transduction andhas a major impact on the development and function of the immune system.Suppressors of cytokine signaling1(SOCS1) is a substaintial intracellular regulator andplay a role as a negative feedback factor for activating of JAK-STAT signaling pathwayand inhibiting of immune responses.In recent years, studies have indicated that SOCS1is associated with SLE. SLE isa complex genetic disease. Genetic background plays crucial roles in the pathogenesisof SLE. Many genes have been found to be associated with SLE susceptibility indifferent populations. Little is known about SOCS1gene polymorphisms andexpressions of SLE in Chinese Han population. Thus, our study adopted a case-controlstudy to assess that SOCS1gene correlated with the development of SLE throughgenetic susceptibility and mRNA expression. We analyzed the relationship amongmRNA expression and single-nucleotide polymorphism (SNP) of the SOCS1gene, andthe main clnical and laboratory features in SLE. Part Ⅰ Association Study of SOCS1Single Nucleotide Polymorphisms withSystemic Lupus ErythematosusObjective To explore SOCS1(SNP rs243324) whether or not confer susceptibility toSLE, and to investigate association between the polymorphisms and the main clnicaland laboratory features in SLE.Methods A total of445patients with SLE were recruited from the First AffiliatedHospital of Anhui Medical University and Anhui Provincial Hospital. All patientsfulfilled the1997revised criteria of the American College of Rheumatology for theclassification of SLE. A total of526healthy blood donors were included as controls, allof whom were excluded from SLE or other autoimmune diseases. Demographic dataand clinical data were collected by questionnaire. EDTA anti-coagulated venous bloodsamples were collected from all participants. Genomic DNA was extracted fromperipheral blood lymphocytes. Genotyping was performed by TaqMan SNP assay. Theprobability level as <0.05in two-tailed test was considered statistically significant.Results(1) HWE testNo deviations from HWE were observed in the cases and controls.(cases: χ~2=0.444,P=0.505; controls: χ~2=2.687, P=0.101).(2) Association analysis of SOCS1gene and SLETo SNP rs243324, genotype frequencies for A/A、A/G and G/G were7.2%,41.6%and51.2%in the case group,5.1%,40.7%and54.2%in the control group, respectively,and no significant differences were showed in the genotype frequencies betweeen them.Allelic distributions for A and G were28.0%,72.0%in the case group and25.5%,74.5%in the control group. No significant differences were either showed in the allelicdistributions betweeen them (P>0.05). (3) Association of SOCS1gene polymorphisms and clinical featuresWhen we analysed SOCS1gene polymorphisms and the main clinical features,such as malar rash, lupus nephritis, arthritis, photosensitivity and oral ulcer, we did notfind any association of clinical features with this SNP in SLE patients (all P>0.05).Conclusions In summary, SOCS1rs243324polymorphism may not contribute to SLEsusceptibility in the Chinese population. Part Ⅱ Association Study of SOCS1mRNA Expressionwith Systemic Lupus ErythematosusObjective To compare the expression of SOCS1mRNA in SLE patients and healthycontrols, LN and SLE without LN, active and inactive SLE. Combined with clinical andlaboratory data, the relationship with their mRNA levels were further analyzed.Methods A total of34patients with SLE and34controls were randomly selected fromsamples of PartⅠ. Individual disease activity was quantified using the systemic lupuserythematosus disease activity index (SLEDAI) scores. RNA was extracted fromperipheral blood lymphocytes. The lever of mRNA expression in PBMC was detectedby relative quantitation PCR. For comparing the median between different groups, thenonparametric Mann-Whitney U two sample tests were used. For the correlationanalysis between SOCS1mRNA and SLEDAI, Spearman’s rank correlation coefficientwas used. The probability level as <0.05in two-tailed test was considered statisticallysignificant. Results(1) SOCS1mRNA expressions in PBMCSOCS1mRNA expressions in PBMC were decreased in SLE patients compared withhealthy controls (P<0.001). Lower SOCS1mRNA expression was also found in theactive SLE patients when compared to inactive counterparties (P=0.015). However,there is no significant difference between LN patients and non-LN SLE patients(P=0.521).(2) Association of SOCS1mRNA expressions and clinical featuresAs for clinical features, SLE patients with photosensitivity showed increased expressionlevel of SOCS1mRNA (P=0.004). However, there is no significant difference betweenSOCS1mRNA expressions and laboratory features (P>0.05).(3) Association of SOCS1polymorphisms and mRNA expressionsWe analysed SOCS1gene (rs243324) polymorphism with mRNA expression among68participants. There is no significant difference between genetypes of the SNP andmRNA expression (P>0.05).Conclusions In summary, SOCS1mRNA expressions in PBMC were decreased in SLEpatients compared with healthy controls. Lower SOCS1mRNA expression was alsofound in the active SLE patients when compared to inactive patients. We detectedsignificant association of SOCS1mRNA expression with part of clinical features. Noassociation was found between the SOCS1gene (rs243324) and mRNA expression.