Association of Midkine and Pleiotrophin Gene Polymorphisms With Systemic Lupus Erythematosus Susceptibility in Chinese Han Population.

In a previous study, we have reported an increased plasma midkine (MK) and pleiotrophin (PTN) concentrations in patients with systemic lupus erythematosus (SLE) and the increase in MK and PTN associated with inflammatory cytokines interleukin (IL)-17 level and some clinical manifestations, suggesting the underlying association of MK and PTN with SLE. This study was conducted to investigate the association between common single-nucleotide polymorphisms (SNPs) in the MK and PTN gene and SLE susceptibility. A total of 989 subjects (496 SLE patients and 493 healthy controls) were included and genotyped for three MK SNPs and seven PTN SNPs in using improved multiple ligase detection reaction (iMLDR). Results have demonstrated no significant differences for genotype and allele frequencies in all 10 SNPs between SLE patients and healthy controls. Case-only analysis in SLE revealed that, in MK gene, the genotype frequency of AA/AG (rs35324223) was significantly lower in patients with photosensitivity than those without; the allele frequency of A/G (rs20542) was significantly higher in patients without serositis. In PTN gene, the A/G allele frequency (rs322236), C/T allele frequency, and TT/CT genotype frequency (rs6970141) showed significantly increased results in patients with immunological disorder compared to those without. Furthermore, no significant differences in plasma MK and PTN concentrations with its SNPs genotypes were found. MK and PTN SNPs showed no associations with SLE genetic susceptibility, but it may be associated with the course of this disease; further studies are needed to focus on the mechanism of MK and PTN genes in the pathogenesis of SLE.

Expression of several long noncoding RNAs in peripheral blood mononuclear cells of patients with systemic lupus erythematosus.

PURPOSE: Accumulating evidence has linked long noncoding RNAs (lncRNAs) to autoimmune and inflammatory disorders. This study aimed to detect the expression levels of five lncRNAs (lnc0640, lnc3643, lnc5150, lnc7514 and lncagf) in peripheral blood mononuclear cells (PBMCs) of patients with systemic lupus erythematosus (SLE), as well as their correlation with clinical and laboratory features. MATERIALS/METHODS: We recruited 76 patients with SLE and 71 normal controls into the present study, and obtained PBMCs from the blood samples of all study subjects. Expression levels of lncRNAs were determined by quantitative real-time reverse transcription polymerase chain reaction and their associations with clinical and laboratory characteristics were analyzed. RESULTS: Lnc5150 expression levels were statistically significantly decreased (Z=-6.016, P < 0.001) compared with normal controls. Lnc3643 levels were also statistically significantly decreased in SLE patients with proteinuria compared with those without (Z=-2.934, P = 0.003), and the lnc7514 levels were statistically significantly lower in anti-dsDNA(+) patients compared with anti-dsDNA(-) patients. The expression levels of lnc3643 were correlated with C-reactive protein and erythrocyte sedimentation rate (ESR), lnc7514 was correlated with disease activity and ESR (all P < 0.01). CONCLUSIONS: The aberrant lncRNA expression levels and their associations with laboratory features in SLE suggest their important role in SLE pathogenesis.

Integrated analysis of lncRNA, miRNA and mRNA expression profiling in patients with systemic lupus erythematosus.

INTRODUCTION: A great deal of research has reported dysregulated expression of genes in systemic lupus erythematosus (SLE). This study aimed to analyze the lncRNA, miRNA and mRNA expression profile in SLE. MATERIAL AND METHODS: RNA sequencing (RNA-seq) was used to detect the dysregulated RNAs in SLE. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways analysis were used to explore the function of these differentially expressed RNAs. RESULTS: 2,353 lncRNAs, 827 mRNAs and 24 miRNAs were shown to be differentially expressed. GO analyses demonstrated that differentially expressed RNAs were enriched in a variety of molecular functions and biological processes including ribonucleotide, protein serine/threonine kinase activity function, regulation of B cell differentiation and others. KEGG pathway analyses revealed that differentially expressed mRNAs and lncRNAs were both enriched in FcγR-mediated phagocytosis, glycosaminoglycan biosynthesis-chondroitin sulfate/dermatan sulfate and glyoxylate and dicarboxylate metabolism pathways. The up-regulated miRNAs target genes were mainly enriched in the nuclear factor-κB (NF-κB) signaling pathway. The down-regulated miRNAs target genes were significantly enriched in metabolism of xenobiotics by cytochrome P450, bile secretion and terpenoid backbone biosynthesis pathways. CONCLUSIONS: The current study reveals a comprehensive expression profile of lncRNAs, miRNAs and mRNAs and implies potential regulatory functions of these RNAs which are involved in the pathogenesis of SLE.

Differentially expressed circular RNAs in systemic lupus erythematosus and their clinical significance.

It has been reported that circRNAs are diff ;erentially expressed in many diseases and can be used as new biomarker to facilitate disease diagnosis. Circular RNAs (circRNAs) microarray were used to identify dysregulated circRNAs in plasma of systemic lupus erythematosus (SLE) patients. Then, we confirmed the microarray data by quantitative reverse transcription polymerase chain reaction (qRT-PCR) in both plasma and peripheral blood mononuclear cells (PBMCs) of SLE. One hundred and twelve circRNAs were identified to dysregulated expressed in plasma of SLE as compared to healthy controls. The results of qRT-PCR showed that the levels of hsa_circRNA_407176 and hsa_circRNA_001308 were decreased in both plasma and PBMCs of SLE when compared with healthy controls. The receiver operating characteristic (ROC) curve area of hsa_circRNA_407176 and hsa_circRNA_001308 in plasma were 0.599 and 0.662, respectively. The area under the ROC curves of hsa_circRNA_407176, hsa_circRNA_406567 and hsa_circRNA_001308 in PBMCs were 0.806, 0.744, and 0.722, respectively. Our study illustrated that hsa_circRNA_407176 and hsa_circRNA_001308 in plasma and PBMCs could be potential biomarkers for SLE.

The expression levels of long noncoding RNAs lnc0640 and lnc5150 and its gene single-nucleotide polymorphisms in rheumatoid arthritis patients.

OBJECTIVES: The aim of our study was to evaluate two lncRNAs (lnc0640 and lnc5150) expressions and gene single-nucleotide polymorphisms (SNPs) in rheumatoid arthritis (RA) patients. METHODS: The expressions of lncRNAs in peripheral blood mononuclear cells (PBMCs) were examined by quantitative real-time reverse transcription polymerase chain reaction from 65 RA patients and 54 controls. Simultaneously, three SNPs (rs13039216, rs6085189, and rs6085190) of lnc0640, three SNPs (rs1590666, rs141561256, and rs144047453) of lnc5150 were genotyped using TaqMan SNP-genotyping assays in 627 RA patients and 590 controls. RESULTS: The lnc0640 level in PBMCs from RA patients was significantly increased (P = 0.001), whereas the lnc5150 level was significantly reduced (P < 0.001) compared to controls. There were significant associations of lnc0640 and lnc5150 levels with C-reactive protein in RA patients (P = 0.011 and P = 0.014, respectively), while lnc5150 level was associated with erythrocyte sedimentation rate (P = 0.022). TT genotype of rs13039216 in lnc0640 gene was statistically associated with a reduced risk of RA (TT vs CC; P = 0.046), and a decreased risk of rs13039216 variant was observed under the recessive model (P = 0.038). In addition, the G allele of rs141561256 polymorphism in lnc5150 gene was significantly associated with rheumatoid factor in RA patients (P = 0.034). There were no associations between lnc0640 and lnc5150 levels and their respective genotype in RA patients. CONCLUSIONS: The expressions of lnc0640 and lnc5150 were alternated in the RA patients, suggesting that these lncRNAs may involve in the development of RA.

Circular RNA expression profile and potential function of hsa_circ_0045272 in systemic lupus erythematosus.

Circular RNAs (circRNAs) represent a class of non-coding RNAs that form covalently closed RNA circles with extensive expression and conservation in mammals. Circular RNAs regulate gene expression through acting as competitive endogenous RNAs (ceRNAs) and modulating gene transcription. Accumulating evidence supports the implication of circRNAs in a variety of human diseases, but studies of circRNA role in systemic lupus erythematosus (SLE) are lacking. The present study measured the circRNA expression profiles in T cells from patients with SLE and healthy controls with human circRNA microarray and identified 127 differentially expressed circRNAs in SLE patients. Down-regulation of hsa_circ_0045272 in SLE T cells was verified with quantitative PCR. Jurkat cells with stable hsa_circ_0045272 knockdown were generated using specific lentiviral short hairpin RNA for functional studies. Flow cytometric analysis indicated that hsa_circ_0045272 knockdown significantly up-regulated the early apoptosis of Jurkat cells. Meanwhile, ELISA showed that hsa_circ_0045272 knockdown significantly enhanced interleukin-2 production of activated Jurkat cells. Then, ceRNAs were predicted for hsa_circ_0045272 and the significant down-regulation of two mRNAs predicted as ceRNAs, NM_003466 (PAX8) and NM_015177 (DTX4), but not their corresponding proteins, was validated. Furthermore, dual luciferase reporter assay indicated binding of hsa_circ_0045272 with hsa-miR-6127. Circular RNA-mRNA co-expression networks showed the correlation of circRNAs with mRNAs and provided additional clues to circRNA functions. Our study demonstrated dysregulated circRNAs in SLE and revealed the function of hsa_circ_0045272 in negatively regulating apoptosis and interleukin-2 secretion and its potential mechanism. The implication of hsa_circ_0045272 and other abnormal circRNAs in SLE merits further investigation.

Meta-analysis of associations between XRCC1 gene polymorphisms and susceptibility to systemic lupus erythematosus and rheumatoid arthritis.

OBJECTIVE: To determine whether X-ray repair cross-complementing group 1 (XRCC1) gene polymorphisms confer susceptibility to systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA). A meta-analysis was conducted to determine the associations between XRCC1 gene polymorphisms and susceptibility to SLE and RA. METHODS: A systematic literature search was conducted to identify all relevant studies. Pooled odds ratios (ORs) with 95% confidence intervals (CIs) were used to estimate the strength of the association. RESULTS: A total of nine case-control articles, consisting of five SLE and four RA articles, involving 1138 patients and 1399 healthy controls, were included in the meta-analysis. This meta-analysis showed no significant association of the Arg399Gln and Arg194Trp polymorphisms with SLE were found in all models when all study subjects were considered together. Stratification by ethnicity indicated the variant Arg399 (A) allele carriers increased the risk of SLE in Asians (A vs. G: OR = 1.402, 95% CI = 1.139-1.726, P = 0.001) and decreased the risk of SLE in Caucasians (A vs. G: OR = 0.769, 95% CI = 0.630-0.937, P = 0.009; AA vs. AG+GG: OR = 0.727, 95% CI = 0.554-0.953, P = 0.021). However, we failed to reveal any association between XRCC1 gene polymorphisms (Arg399Gln, Arg280His and Arg194Trp) and RA risk under all analysis models. Similar results were obtained in the subgroup analysis based on ethnicity. CONCLUSIONS: The present study suggests that the XRCC1 Arg399Gln polymorphism might be associated with genetic susceptibility to SLE in Asians and Caucasians, and there is no significant association between XRCC1 gene polymorphisms (Arg399Gln, Arg280His and Arg194Trp) and RA risk.

Comprehensive long non-coding RNA expression profiling reveals their potential roles in systemic lupus erythematosus.

Long non-coding RNAs can regulate gene transcription, modulate protein function, and act as competing endogenous RNA. Yet, their roles in systemic lupus erythematosus remain to be elucidated. We determined the expression profiles of lncRNAs in T cells of SLE patients and healthy controls using microarrays. Up to 1935 lncRNAs and 1977 mRNAs were differentially expressed. QRT-PCR showed downregulated uc001ykl.1 and ENST00000448942 in SLE patients. Expression of uc001ykl.1 correlated with erythrocyte sedimentation rate (ESR) and C-reactive protein, whereas ENST00000448942 level correlated with ESR and anti-Sm antibodies. Short time-series expression miner analysis revealed some lncRNAs whose expressions might correlate with disease activity of SLE patients. Coding-non-coding gene coexpression analyses showed differential lncRNAs might operate via modulating expressions of their correlated, relevant mRNAs in SLE. Differential lncRNAs might also function through their ceRNAs. Our study established that the aberrant expression profiles of lncRNAs may play a role in SLE and thus warrant further investigation.

Relationship between the IL12B (rs3212227) gene polymorphism and susceptibility to multiple autoimmune diseases: A meta-analysis.

OBJECTIVES: The purpose of this study was to evaluate whether a single-nucleotide polymorphism (SNP) IL12B 3(')UTR +1188A/C (rs3212227) confers susceptibility to several autoimmune diseases. METHODS: A systematic literature search was conducted to identify relevant studies. Pooled odds ratio (OR) with 95% confidence interval (CI) was used to estimate the strength of association. RESULTS: Twenty-five studies were included in the meta-analysis, which contained 9794 cases and 11,330 controls. Our result indicated that IL12B +1188A/C (rs3212227) polymorphism was associated with type-1 diabetes (T1D) in the dominant model (p = 0.008), and an increased risk was found in East Asians in the dominant model (p < 0.001). East Asians rheumatoid arthritis (RA) patients seemed to be at risk of allelic model (p = 0.011). As to Behcet's disease (BD), there was a risk in dominant model (p = 0.020) and positive associations of dominant model, allelic model in East Asians (p = 0.009; p < 0.001, respectively). But we failed to find any association between IL12B +1188A/C (rs3212227) polymorphism with Graves' disease (GD) and ankylosing spondylitis (AS). CONCLUSIONS: The present study suggests that the IL12B +1188A/C (rs3212227) polymorphism might be associated with genetic susceptibility to autoimmune diseases, such as T1D, RA, BD, but not GD and AS.

A front-end automation tool supporting design, verification and reuse of SOC.

This paper describes an in-house developed language tool called VPerl used in developing a 250 MHz 32-bit high-performance low power embedded CPU core. The authors showed that use of this tool can compress the Verilog code by more than a factor of 5, increase the efficiency of the front-end design, reduce the bug rate significantly. This tool can be used to enhance the reusability of an intellectual property model, and facilitate porting design for different platforms.