Polymorphisms In Systemic Lupus Erythematosus Research Articles

ICOS gene polymorphisms in systemic lupus erythematosus: A case-control study.

The inducible T-cell costimulator (ICOS) may play an important role in adaptive immunity by regulating the interaction between T cells and antigen-presenting cells. Disruption of this molecule can lead to autoimmune diseases, in particular systemic lupus erythematosus (SLE). In this study, we aimed to explore the possible association between ICOS gene polymorphisms and SLE as well as their influence on disease susceptibility and clinical outcomes. A further objective was to assess the potential impact of these polymorphisms on RNA expression. A case-control study, including 151 patients with SLE, and 291 unrelated healthy controls (HC) matched in gender, and geographical origin, was performed to genotype two polymorphisms located in the ICOS gene: rs11889031 (-693 G/A) and rs10932029 (IVS1+173 T/C); using the polymerase chain reaction (PCR)-restriction fragment length polymorphism method. The different genotypes were validated by direct sequencing. The expression level of ICOS mRNA was assessed by quantitative PCR in peripheral blood mononuclear cells of SLE patients and HC. The results were analysed using Shesis and spss.20. Our results revealed a significant association between ICOS gene rs11889031>CC genotype and SLE disease (codominant genetic model 1, (C/C vs. C/T), p=.001, odds ratio [OR]=2.18 IC [1.36-3.49]); codominant genetic model 2, (C/C vs. T/T) p=.007, OR=15.29 IC [1.97-118.5]); dominant genetic model, (C/C vs. C/T+T/T) p=.0001, OR=2.44 IC [1.53-3.9]). Besides, there was a marginal association between rs11889031>TT genotype and T allele with a protective role from SLE (recessive genetic model, p=.016, OR=0.08 IC [0.01-0.63] and p=7.6904E-05, OR=0.43 IC=[0.28-0.66], respectively). Moreover, statistical analysis indicated that the rs11889031>CC genotype was linked with clinical and serological manifestations of SLE, including blood pressure, and anti-SSA antibodies production in SLE patients. However, the ICOS gene rs10932029 polymorphism was not associated with susceptibility to SLE. On the other side, we did not note any effect of the two selected polymorphisms on the level of ICOS mRNA gene expression. The study showed a significant predisposing association of the ICOS rs11889031>CC genotype with SLE, in contrast to a protective effect of rs11889031>TT genotype in Tunisian patients. Our results suggest that ICOS rs11889031 may act as a risk factor for SLE and could be used as a genetic susceptibility biomarker.

Role of HLA alleles polymorphism in systemic lupus erythematosus: A prospective study from North India.

Systemic lupus erythematosus (SLE) is a chronic autoimmune disorder and has complex etiopathogenesis. The most appropriate hypothesis states that genetic susceptibility in the presence of environmental risk factors predisposes to SLE. HLA class II alleles are critical to immune response and are highly polymorphic. Various alleles in HLA-DR and -DQ regions were analyzed in SLE patients and healthy controls to see their role in susceptibility or protection to SLE. This was a prospective observational study, in which a total of 100 SLE patients and 100 controls were analyzed. HLA typing was done by polymerase chain reaction (PCR)-sequence-specific oligonucleotide (SSO) method (SSO probe). DRβ1*0301 was significantly increased in SLE patients when compared to controls and had the highest odds ratio. Other risk factor alleles found to be increased were DRβ1*0701, DQβ1*0202, and DQβ1*0301, which had a significant positive association with SLE, suggesting their role in susceptibility to SLE. In contrast, DRβ1*0401, DRβ1*1401, DRβ1*1404, DRβ1*1501, DQβ1*0501, and DQα1*0201 showed statistically significant reduction in SLE patients, while these were much more common in controls, suggesting their protective role. This study is only the second study in patients from North India and it determines the role of DRβ1*0301, DRβ1*0701, DQβ1*0202, and DQβ1*0301 alleles as risk factors in SLE patients.

Protective role of T regulatory (Treg) cells in systemic lupus erythematosus patients with nephritis

AimTo assess the role of CD4+CD25+Foxp3+, CD4+CD25- Foxp3+, CD4+CD25+Foxp3- T cells and the fork head family transcription factor (Foxp3) gene polymorphism in systemic lupus erythematosus (SLE) and lupus nephritis (LN) patients. Patients and methodsThe study comprised 40 SLE patients (including 38 females and 2 males) and 30 matched controls. SLE disease activity index (SLEDAI) was assessed. The percentage of expression of CD4, CD25 and Foxp3 on T cells was measured by flow cytometry. Foxp3 gene was genotyped using the polymerase chain reaction–restriction fragment length polymorphism (PCR-RFLP). ResultsThe patients were 38 females and 2 males with a mean age of 30.3±8.9 years and disease duration of 7.4±5.7 years. Their mean SLEDAI was 7.5±6.7. Flow cytometry revealed 3 types of T cells; CD4+CD25+Foxp3+, CD4+CD25- Foxp3+ and CD4+CD25+Foxp3-. No significant differences were found in the percentage of expression and absolute counts of CD4+CD25+Foxp3+, CD4+CD25- Foxp3+ and CD4+CD25+Foxp3- T cells in patients and controls (p=0.26, p=0.22, p=0.32 respectively). CD4+CD25+Foxp3+T cells were significantly lower in patients with LN compared to those without (p<0.001). CD4+CD25- Foxp3+ T cells and Foxp3 (G/G) genotype were significantly associated with the grades of LN (p<0.001, p=0.003 respectively). The relationship between SLEDAI and the absolute counts of CD4+CD25+Foxp3+, CD4+CD25- Foxp3+ and CD4+CD25+Foxp3- T cells was insignificant (r=−0.04, p=0.78; r=0.05, p=0.76 and r=0.05, p=0.77 respectively). A significant difference in SLEDAI between patients expressing Foxp3 A/A genotype and those not was observed (p<0.01). ConclusionCD4+CD25+Foxp3+, CD4+CD25- Foxp3+ and CD4+CD25+Foxp3- T cells are important regarding the pathogenesis of LN and could help assess the severity of renal involvement.

Polymorphism in STAT4 Increase the Risk of Systemic Lupus Erythematosus: An Updated Meta-Analysis.

Previous studies have reported that STAT4 rs7574865 conferred the susceptibility to systemic lupus erythematosus (SLE). In this study, a meta-analysis (including 32 comparative studies of 11384 patients and 17609 controls) was conducted to investigate the role of STAT4 polymorphism in SLE in a comprehensive way. We found that the Asian population had the highest prevalence of the T allele than any other study population at 32.2% and that STAT4 rs7574865 polymorphism was associated with SLE in the overall population (OR = 1.579, 95%CI = 1.497-1.665, P < 0.001). In the subgroup analysis by ethnicity, STAT4 rs7574865 T allele was shown to be risk factor in SLE in Asian, European, and American origins. Our results do support STAT4 rs7574865 polymorphism as a susceptibility factor for SLE in populations of different ethnic and that its prevalence is ethnicity dependent.

Interleukin 17A rs2275913 polymorphism is associated with susceptibility to systemic lupus erythematosus: A meta and trial sequential analysis.

The role of cytokines in the development of systemic lupus erythematosus (SLE) has received much attention. Interleukin-17A upregulates several inflammation-related genes and is thought to have a crucial role in SLE development. The susceptibility to SLE development has been linked to functional genetic variations of the IL-17A gene; nevertheless, the findings have been conflicting. We conducted a meta-analysis that included previously published reports to establish a definitive conclusion on the role of the IL-17A rs2275913 polymorphism in SLE propensity. The PubMed, Google Scholar, and Scopus databases were used to find eligible published articles. All analyses were conducted using Comprehensive Meta-analysis V3.1. Funnel plots and Egger's regression analysis were used to assess publication bias. Q statistics and I2 test explored the heterogeneity among the included studies. Combined odds ratio, 95% confidence interval were calculated for each comparison model. Based on the inclusion and exclusion criteria, a total of four reports, comprising of 608 SLE patients and 815 healthy controls, were considered for the present meta-analysis. The homozygous comparison (AA vs. GG: combined odds ratio= 2.046, p = 0.005) and recessive genetic model (AA vs. GG+GA: combined odds ratio=1.901, p = 0.010) analysis revealed a significant association of rs2275913 with susceptibility to the development of SLE. However, other genetic comparisons (A vs. G, GA vs. GG, AA+GA vs. GG) failed to demonstrate such association. Furthermore, trial sequential analysis revealed a sufficient number of studies, including enough cases and controls that have already been considered to conclude the role of IL17-A rs2275913 polymorphism in SLE. IL-17A rs2275913 polymorphism is associated with susceptibility to SLE development.

Annexin A1 and its receptor gene polymorphisms in systemic lupus erythematosus in the Tunisian population.

An association between ANXA1, FPR1 and FPR2 gene polymorphisms and the patho-physiology of many human diseases was suggested by numerous studies. Our study aimed to evaluate association between common polymorphisms in the 9q21.13 and 19q13.41 and susceptibility to systemic lupus erythematosus (SLE) in the Tunisian population. We performed a case-control study on 107 Tunisian SLE patients and 122 healthy controls to explore 9 polymorphisms of the three studied genes: rs2811226 and rs3739959 (ANXA1), rs5030880, rs1042229, rs1461765570, rs17849971, rs867228 (FPR1), rs17694990 and rs11666254 (FPR2). Four polymorphisms were found to be linked with SLE susceptibility: rs3739959-ANXA1 > G and GG (p = 0.021, OR = 1.73 and p = 0.014, OR = 2.06 respectively), rs867228-FPR1 > TT (p = 0.014, OR = 4.59), rs11666254-FPR2 > GG (p = 0.019, OR = 8.34) and rs17694990-FPR2 > T (p = 0.05, OR = 1.506). In homogenous groups of SLE patients depending on clinical manifestations and serological results, previous associations were confirmed with a panoply of manifestations of lupus including lupus nephritis, malar rash, mouth ulceration and hypocomplementia. Our study showed an association between ANXA1 > rs3739959, FPR1 > rs867228, FPR2 > rs11666254, FPR2 > rs17694990 and SLE susceptibility. Our results also showed a strong association between the two ANXA1 studied SNPs and LN which allowed us to suggest these two SNPs as biomarkers of LN development in SLE. Further research is needed to understand by which mechanism the gene variants affect susceptibility to SLE. Key Points • Lupus erythematosus is an autoimmune disease in which a panoply of factors are implicated • Annexin A1 interaction with its receptors are suggested as a target in therapy of a panoply of human disease in particular cancers • The present results highlighted the implication of Annexin A1 and its receptors gene polymorphisms in the physiopathology of lupus, in particular in the involvement of renal and cutaneous lesions.

Levels of the macrophage migration inhibitory factor and polymorphisms in systemic lupus erythematosus: a meta-analysis.

IntroductionSeveral published results have established variations in respect to plasma/serum macrophage migration inhibitory factor (MIF) levels and gene polymorphisms with systemic lupus erythematosus (SLE). This study gave a more concise estimation on the MIF levels for SLE patients and established the association between MIF polymorphisms and SLE.Material and methodsAll articles were searched from PubMed, Embase, Web of Science, Wan-Fang, Chinese Biological Medical Literature, and China National Knowledge Infrastructure up to 6th October 2017, with no language restriction. Pooled standard mean difference with 95% confidence interval was evaluated using random effect model. Thirteen articles were used for this meta-analysis, with 620 SLE patients and 779 healthy controls assessed for MIF levels, and 2,159 SLE patients and 2,574 healthy controls considered for MIF-173 C/G and MIF-794 CATT polymorphisms.ResultsThere was a significant higher MIF levels in SLE patients than in healthy controls (p = 0.004). The subgroup analysis showed Asians and ages < 30 had higher MIF levels in SLE patients than in healthy controls. It was evident that patients with systemic lupus erythematosus diseases activity index scores < 8 and ≥ 8, and disease duration for both year < 5 and ≥ 5 of SLE had higher MIF levels when compared to healthy controls. We found a significant association between SLE and MIF-173 C/G, but not MIF-794 CATT.ConclusionsThis study provided evidence of significant higher MIF levels in SLE patients and supported the association of MIF-173 C/G and SLE. However, we were not able to establish an association between MIF-794 CATT and SLE.

Association of CD40 Gene Polymorphisms With Systemic Lupus Erythematosus and Rheumatoid Arthritis in a Chinese Han Population.

Systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA) are complex autoimmune diseases. CD40 participates in inflammatory response, and promotes fibroblast proliferation, leading to occurrence and progression of SLE, RA. This study explores CD40 gene polymorphisms in SLE and RA patients from a Chinese Han population. Two hundred SLE patients, 340 RA patients, and 900 healthy controls were enrolled. Genomic DNA was extracted from peripheral blood, and six polymorphisms of CD40 gene (rs3765456, rs1569723, rs73115010, rs13040307, rs1883832, and rs4810485) were detected by KASP method. Frequencies of rs1569723 genotypes AA, AC, AA+AC were significantly higher in RA patients as compared to those in healthy controls (P = 0.049, P = 0.024, P = 0.022). Frequencies of genotypes CT, CC+CT of rs1883832, and GT, GG+GT of rs4810485 were significantly higher in RA patients as compared to those in healthy controls (P = 0.012, P = 0.018, P = 0.009, P = 0.015). RA patients carrying rs13040307 C allele and rs73115010 T allele showed increased number of swollen joints. Moreover, frequency of allele T of rs13040307 was lower in SLE patients with positive anti-dsDNA and hematuria as compared to that in patients without these parameters (P = 0.038, P = 0.045). There were increased frequencies of genotype TT, allele T for rs13040307 and lower frequencies of genotype TT, allele T for rs73115010 in lupus patients with myositis (all P<0.05). Interestingly, frequencies of rs1569723 A allele, rs4810485 T allele were higher in SLE patients with myositis, and frequencies of rs3765456 A allele, rs1883832 T allele were lower in SLE patients with myositis (All P<0.05). In conclusion, CD40 gene polymorphisms may associate with susceptibility to SLE and RA.

Association of signal transducer and activator of transcription 4 gene (restriction site7582694) single nucleotide polymorphism with systemic lupus erythematosus

Background — Systemic lupus erythematosus (SLE) is an inflammatory autoimmune disease characterized by production of autoantibodies and deposition within various organs. The incidence of SLE averages 5 cases per 100,000 population. Various genome wide studies have shown association of STAT4 (signal transducer and activator of transcription 4) gene with SLE and lupus nephritis (LN). Therefore, this study was designed to determine single nucleotide polymorphism (SNP) in STAT4 (rs7582694) in local SLE, LN patients and healthy controls. Objective — To determine the frequency of STAT4 (rs7582694) gene polymorphism in systemic lupus erythematosus, lupus nephritis patients and healthy controls. Methods — It was a case-control study. Eighty samples were recruited for each of two study groups. Deoxyribonucleic acid (DNA) extraction was carried out using standard phenol chloroform method. Further, samples were processed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) conventional technique and genotypes were determined. Polymorphism analysis and allele frequencies were compared between groups using the chi-square test. Project was approved by the Ethical Review Board at the University of Health Sciences, Lahore, Pakistan. Results — Females were more inclined towards developing SLE. The study unveiled that SNP in STAT 4 gene (rs7582694) was associated with SLE patients in Pakistani population which indicates that this may play a role in susceptibility to SLE. Moreover, we infer that genetic variations within STAT4 (rs7582694) predispose patients to lupus nephritis. It was also evident that GG and GC genotypes were more susceptible of further transforming into SLE and LN. Conclusion: The findings of this study may contribute to a better understanding of underlying etiological and prognostic factors regarding SLE and LN.

Association of tumor necrosis factor alpha-induced protein 3 gene polymorphism and systemic lupus erythematosus

Background Tumor necrosis factor-alpha-induced protein 3 (TNFAIP3) is a negative regulator of the activity of NF-κB in the cells and genetic variations in TNFAIP3 may be implicated in the risk of systemic lupus erythematosus (SLE) development.Objective The purpose of this paper is to evaluate TNFAIP3 gene polymorphism in SLE and its relationship with autoimmune parameters.Methods The study was carried out on 94 children suffering from SLE and 94 healthy controls of matched age and sex. TNFAIP3 polymorphism by RT-PCR using TaqMan assay, and levels of serum antinuclear and serum anti-double-stranded DNA were measured by ELISA technique. Complement C3 and C4 were estimated by using turbidimetric assay.Results The results showed that there is no significant correlation of TNFAIP3 alleles or genotypes with risk of development of SLE (P>0.05). In addition, the authors did not detect any significant correlation between alleles or genotypes of TNFAIP3 with SLE clinical features and immune disorders (P>0.05).Conclusion The authors concluded that TNFAIP3 polymorphism is not associated with SLE risk. In addition, these results suggested no significant association between the TNFAIP3 SNP and autoimmune parameters, or any complications among SLE individuals.

Role of serum leptin levels and leptin receptor gene polymorphisms in systemic lupus erythematosus.

Serum leptin and leptin receptor gene polymorphisms may play a role in the etiopathogenesis of SLE. This study was undertaken to explore the relationship between serum leptin levels and leptin receptor (LEPR) gene polymorphisms with susceptibility to SLE in Egyptian population and to study their relationships with clinical, laboratory, radiographic findings, and disease activity of SLE (SLEDAI). A total of 50 unrelated female patients, who met the SLICC classification criteria for SLE and fifty healthy blood donors, matched for age, sex, and BMI with SLE patients, serving as a control group, were included in this study. All participants had completed preliminary questionnaires and clinical, laboratory, and radiographic examinations. Serum leptin levels were measured by ELISA assays. LEPR genotyping was done by polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP) method. We compared serum leptin levels and LEPR gene polymorphisms in SLE patients and controls, and we tested their relationships with clinical, laboratory, and radiographic findings and SLEDAI in SLE patients. The present study showed significant differences of serum leptin levels between SLE patients and controls (p < 0.001). Moreover, higher frequencies of variant genotype (AA) and (A) allele were found in SLE patients compared to controls (p = 0.008 and 0.001, respectively). No associations were observed between the serum leptin, various LEPR genotypes, and gene alleles and the development of clinical, laboratory, and radiological manifestations. Furthermore, no associations were observed between the various LEPR genotypes or gene alleles and leptin levels (p = 0.633 and 0.337 respectively) in SLE patients. Additionally, no correlations were observed between leptin levels, various genotypes, and alleles with SLEDAI (p = 0.244, 0.741, and 0.838 respectively) in SLE patients. Serum leptin and LEPR gene polymorphism increase risk of SLE in Egyptian population; however, they are not associated with the development of clinical, lab, and radiological findings. Disease activity is neither correlated with serum leptin level nor associated with LEPR gene polymorphism. Serum levels of leptin are not associated with LEPR gene polymorphism. Key Points • Serum leptin and LEPR gene polymorphism increase risk of SLE in Egyptian patients. • Serum leptin is not associated with SLE disease activity.

Assessment of circulating MCP-1 level and 2518A&gt;G gene polymorphism in systemic lupus erythematosus

Lupus nephritis (LN) is a major contributor to morbidity and mortality in patients with Systemic Lupus Erythematosus (SLE). This study aims to investigate the possible role of a functional polymorphism in the regulatory region of the monocyte chemo-attractant protein-1 (MCP-1) gene and MCP-1 blood level in the diagnosis of LN and in correlating the MCP-1 blood levels with disease activity. The study included 56 SLE patients and 56 controls. All the SLE patients suffered from LN. An analysis of MCP-1 gene polymorphism by polymerase chain reaction was performed followed by restriction fragment length polymorphism (PCR-RFLP) analysis and MCP-1 blood level was determined using the ELISA technique. Calculation of Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) was performed. Serologic tests included the determination of antinuclear antibody (ANA) and anti-double-stranded (ds) DNA antibodies, Complement C3 and C4 levels. A significant increase in the frequency of genotype A/G and a decrease in the frequency of genotype A/A were found among patients with active LN compared to inactive LN. There was a statistically significant difference in the blood level of MCP-1 between LN patients and controls. Also, MCP-1 blood levels were significantly higher in active LN patients than inactive LN. A significant positive linear correlation was detected between MCP-1 blood level and SLEDAI, creatinine, and 24 hours protein in LN patients. These results suggest that an A/G genotype together with the measurement of the blood level of MCP-1 can be a useful tool for detection and follow up of active LN.&#x0D;

Associations between paraoxonase-1 and systemic lupus erythematosus.

The objective of this analysis was to explore associations between paraoxonase-1 levels, gene polymorphisms and systemic lupus erythematosus. Meta-analyses of paraoxonase-1 levels and Q192R and L55M and polymorphisms in systemic lupus erythematosus were conducted. Nine articles were incorporated in our meta-analysis, which uncovered that the paraoxonase-1 level was decreased in systemic lupus erythematosus compared to control (standard mean difference = -1.626, 95% confidence interval = -2.829--0.424, p = 0.008). Ethnicity-specific meta-analysis demonstrated a relation tendency between decreased paraoxonase-1 activity and lupus in Europeans (standard mean difference = -1.236, 95% confidence interval = -2.634-0.163, p = 0.083). Paraoxonase-1 activity was reduced in systemic lupus erythematosus in a single Arab and African population. Decreased paraoxonase-1 activity was found in a small sample of systemic lupus erythematosus patients (standard mean difference = -1.642, 95% confidence interval = -3.076--0.247, p = 0.021). Ethnicity-specific analysis indicated a relationship between the paraoxonase-1 55 M allele in the Arab systemic lupus erythematosus population. However, a lack of association with systemic lupus erythematosus and the paraoxonase-1 192 R allele was observed. Meta-analyses revealed reduced paraoxonase-1 activity in patients with systemic lupus erythematosus and found possible associations between systemic lupus erythematosus and paraoxonase-1 L55M polymorphism in a specific ethnic group.

Role of CTLA4 A49G polymorphism in systemic lupus erythematosus and its geographical distribution

CTLA-4 (cytotoxic T-lymphocyte-associated protein-4) or CD152 is an inhibitory receptor expressed constitutively on CD4+ CD25+ T regulatory lymphocytes and transiently on activated CD4+ and CD8+ T lymphocytes. Its inhibitory function...

Plasminogen activator inhibitor-1 gene polymorphisms in systemic lupus erythematosus: is there a risk for lupus nephritis among Egyptians?

Background Systemic lupus erythematosus (SLE) is a systemic autoimmune disease characterized by immune complexes formation and body organs damage. Recently, plasminogen activator inhibitor-1 (PAI-1) has been proposed recently to modulate the immune response. Aim of the study To elucidate whether there is possible role of two genetic polymorphisms in the PAI-1 gene: −675 4G/5G and HindIII C>G in lupus nephritis (LN) disease in Egyptian patients. Patients and methods Using PCR-restriction fragment length polymorphism, we genotyped 170 Egyptian patients with SLE; 80 fulfill the American College of Rheumatology criteria of LN and 90 SLE patients without LN for two polymorphisms of PAI-1 gene: −675 4G/5G and HindIII C>G. Results The 4G4G genotype, 4G allele of PAI 4G/5G polymorphism, and the G allele of the PAI-1 HindIII C>G polymorphism, all exhibited significant risks for proliferative LN [odds ratio (OR)=2.55; 95% confidence interval (CI): 1.02–21.11; P=0.022); (OR=2.43; 95% CI: 1.18–5.01; P=0.015); (OR=2.37; 95% CI: 1.01–5.58; P=0.045), respectively]. Moreover, PAI-1 4G/5G polymorphism was related to the chronicity index for LN (P G polymorphism was associated with the activity (P=0.016) and the chronicity (P Conclusion Egyptian patients with SLE with a polymorphism for −675 4G/5G and HindIII C>G of PAI-1 gene might have a higher susceptibility for the development of proliferative LN.

Association of long noncoding RNAs expression levels and their gene polymorphisms with systemic lupus erythematosus

Increasing evidence has demonstrated the association between long noncoding RNAs (lncRNAs) and multiple autoimmune diseases. To explore four lncRNAs (GAS5, lnc-DC, linc0597 and linc0949) expression levels and gene polymorphisms in systemic lupus erythematosus (SLE), a two stage design was applied. In the first stage, 85 SLE patients and 71 healthy controls were enrolled to investigate the lncRNAs expression levels. Then, 1260 SLE patients and 1231 healthy controls were included to detect the single nucleotide polymorphisms (SNPs) in the differentially expressed lncRNAs identified in the first stage. Linc0597, lnc-DC and GAS5 expression levels were significantly lower in SLE patients than healthy controls (P < 0.001, P < 0.001, P = 0.003 respectively). Association of five SNPs (rs10515177, rs2070107, rs2632516, rs2877877, rs2067079) with SLE risk were analyzed. No significant association was observed between these gene polymorphisms and susceptibility to SLE (all P > 0.010), and we did not find significant association between any genotypes at five SNPs and their respective lncRNAs expression in SLE (all P > 0.010). In summary, the expression levels of linc0597, lnc-DC and GAS5 are decreased in SLE patients, but their gene polymorphisms are not associated with SLE risk, and do not influence their expression levels.

Circulating macrophage migration inhibitory factor levels and its polymorphisms in systemic lupus erythematosus: A meta-analysis.

The present study aimed to systemically review the evidence regarding the relationship between circulating macrophage migration inhibitory factor (MIF) levels and systemic lupus erythematosus (SLE), as well as the associations between several polymorphisms in the MIF gene and SLE susceptibility. We performed a meta-analysis of serum/plasma levels of MIF in SLE patients and controls and evaluated evidence of associations between the MIF -173 C/G allele and -794CATT5-8 polymorphisms and the associated risk for SLE. Nine studies were included in this meta-analysis. Meta-analysis indicated that MIF levels were significantly higher in the SLE group than in the control group (SMD = 1.154, 95% CI = 0.369-1.938, P = 0.004). Stratification by ethnicity showed significantly higher MIF levels in the SLE group representing Asian populations (SMD = 1.911, 95% CI = 0.871-2.951, P &lt; 0.001). MIF levels were significantly higher in the SLE group than in the control group in the age-and/or sex matched population, but not in the unmatched population (SMD = 1.236, 95% CI = 0.579-1.893, P &lt; 0.001; SMD = 1.118, 95% CI = -0.027-2.263, P = 0.056). However, results of the meta-analysis showed no association between SLE and the MIF -173 C allele, the -794CATT7 allele, and the -794CATT7-MIF-173C haplotype with high heterogeneity. Our meta-analysis demonstrated significantly higher circulating MIF levels in patients with SLE, but no evidence of associations between MIF -173 C/G and -794CATT5-8 polymorphisms and SLE susceptibility.

Relationship between rs1801157 polymorphism in stromal cell-derived factor gene and systemic lupus erythematosus risk.

ObjectivePresent meta-analysis was performed to investigate the role of stromal cell-derived factor (SDF-1) gene rs1801157 polymorphism in systemic lupus erythematosus (SLE).ResultsFive publications with 1,087 cases and 1,181 controls were incorporated in this meta-analysis. Overall, a marginal association between SDF-1 rs1801157 polymorphism and reduced SLE risk was found under GA vs. GG model (OR = 0.84, 95% CI = 0.70–1.00). A similar result was also observed in Asian subgroup under the same comparison after stratification analysis by ethnicity (OR = 0.79, 95% CI = 0.63–1.00).Materials and MethodsAll included studies were retrieved from PubMed, EMBASE, Google Scholar Web and Chinese National Knowledge Infrastructure (CNKI). Odds ratios (ORs) with 95% confidence intervals (95% CIs) were calculated to appraise the strength of association between SDF-1 rs1801157 polymorphism and SLE risk. The stratification analysis was also performed according to ethnicity. In addition, heterogeneity was examined with Q test, and sensitivity analysis was used to test the stability of final results. Begg’s funnel plot and Egger’s test were adopted to evaluate publication bias.ConclusionsSDF-1 rs1801157 polymorphism may not influence the risk of SLE. However, more studies with larger sample sizes involving different populations are needed to further explore this issue.

Clinical significance of tumor necrosis factor-α-863 C/A and -1031 T/C promoter polymorphisms in systemic lupus erythematosus patients: Relation to disease activity and damage

Aim of the workTo assess the clinical significance of serum levels of tumor necrosis factor alpha (TNF-α) and its -863 C/A and 1031 T/C promoter polymorphism in systemic lupus erythematosus (SLE) patients and find any association to disease activity and damage. Patients and methodsForty-two female SLE patients and 30 age and gender matched healthy control were included. Systemic Lupus Erythematosus Disease Activity Index and the Systemic Lupus International Collaboration Clinics-damage index were assessed. Serum TNF-α levels were measured and genotyped for TNF-α-863 C/A and 1031 T/C promoters. ResultsThe SLE patients had a mean age of 28.5±7.6years and disease duration 3.3±2.9years. The mean serum TNF-α level in the SLE patients (8.2±9.8pg/ml) was significantly higher than in the control (3.5±2.6pg/ml) (p=0.005). The TNF-α-863AA genotype was significantly frequent (52.4%) in the SLE patients compared to control (23.3%) (p=0.012). Those patients had a significantly increased proteinuria and a tendency to a higher serum TNF-α level. Patients with TNF-α-1031 CC genotype had a significantly increased serum TNF-α levels (p=0.002) and frequency of mucocutaneous manifestations (p=0.03) as well as a higher frequency of lupus nephritis (LN) compared to those with TT genotype (p=0.04). Only serum TNF-α level would predict the disease activity. ConclusionTNF-α-863 promoter gene polymorphism may be considered as a genetic marker for SLE susceptibility and its AA genotype was associated with LN and with high serum TNF-α production. The TNF-α-1031 AA genotype was related to an increased serum TNF-α level as well as to mucocutaneous manifestations and LN.

Association between circulating transforming growth factor-β1 level and polymorphisms in systemic lupus erythematosus and rheumatoid arthritis: A meta-analysis.

This study systemically reviewed evidence regarding the relationship between circulating blood transforming growth factor-β1 (TGF-β1) levels and systemic lupus erythematous (SLE) and rheumatoid arthritis (RA), and associations between TGF-β1 polymorphisms and susceptibility to SLE and RA. We conducted a meta-analysis on the serum/plasma TGF-β1 levels in SLE and RA patients and healthy controls, and the associations between TGF-β1 +869 T/C, +915 C/G, and -509 T/C polymorphisms and SLE or RA risk. Twenty-eight studies were considered in this meta-analysis. Circulating TGF-β1 levels were significantly lower in the SLE group than in controls (SMD = -1.164, 95% CI = -2.257 - -0.070, P = 0.037). Serum/plasma TGF-β1 levels were not significantly different between RA and control groups (SMD = 0.699, 95% CI = -0.379 - 1.717, p = 0.211). No association between TGF-β1 +869 T/C polymorphism and SLE was found. However, meta-analysis showed an association between the TGF-β1 +869 T allele and RA in all subjects (OR = 1.282, 95% CI = 1.118-1.470, P = 3.8 x 10-4). Analysis after stratification by ethnicity indicated that the T allele was significantly associated with RA in Asians and Arabs (OR = 1.429, 95% CI = 1.179-1.733, P = 2.9 x 10-4; OR = 1.352, 95% CI = 1.097-1.668, P = 0.005), but not Europeans. However, no association was found between TGF-β1 +915 G/C or -509 C/T polymorphisms and RA or SLE. Meta-analysis revealed a significantly lower circulating TGF-β1 level in SLE patients, and a significant association between TGF-β1 +869 T/C polymorphism and RA development.