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Hong-Miao Li,1 Fei Tang,2 Qian Huang,3 Hai-Feng Pan,1 Tian-Ping Zhang4 1Department of Epidemiology and Biostatistics, School of Public Health, Anhui Medical University, Hefei, People’s Republic of China; 2Department of Interventional Pulmonology and Endoscopic Diagnosis and Treatment Center, Anhui Chest Hospital, Hefei, People’s Republic of China; 3Department of Public Health, Medical Department, Qinghai University, Xining, People’s Republic of China; 4The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, People’s Republic of ChinaCorrespondence: Tian-Ping Zhang, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, People’s Republic of China, Email zhangtianping@ustc.edu.cn Hai-Feng Pan, Department of Epidemiology and Biostatistics, School of Public Health, Anhui Medical University, Hefei, People’s Republic of China, Email panhaifeng1982@sina.comObjective: Our study aimed to explore the association of IL-13, IL-13RA1, and IL-13RA2 genes polymorphisms with PTB susceptibility and its clinical features.Methods: Nine SNPs were genotyped by improved multiple ligase detection reaction (iMLDR) in 476 PTB patients and 473 controls. The association between these SNPs and PTB risk was analyzed using SPSS software and haplotype analysis was assessed using SHEsis software.Results: The IL-13RA1 rs2495636 GA genotype frequency in PTB patients was significantly decreased, and IL-13RA2 rs5946039 A allele was related to the lower risk of PTB. In IL-13 gene, rs20541 variant was found to be associated with PTB risk under recessive mode. Moreover, IL-13RA1 rs141573089 C allele was significantly lower in PTB presenting with fever, drug resistance, and CC genotype was decreased in PTB presenting with leukopenia. IL-13RA1 rs2495636 polymorphism was associated with drug resistance, pulmonary infection, and IL-13RA2 rs3795175, rs638376 polymorphisms were related to drug resistance in PTB patients.Conclusion: IL-13 rs20541, IL-13RA1 rs2495636, IL-13RA2 rs5946039 polymorphisms might be contributed to the genetic background of PTB in Chinese population.Keywords: pulmonary tuberculosis, Mycobacterium tuberculosis, interleukin-13, single nucleotide polymorphisms

Hong-Miao Li,1,2 Qian Huang,1 Fen Tang,2 Tian-Ping Zhang3 1Department of Epidemiology and Biostatistics, School of Public Health, Anhui Medical University, Hefei, 230032, Anhui, People’s Republic of China; 2Anhui Chest Hospital (Anhui Provincial TB Institute), Hefei, 230022, Anhui, People’s Republic of China; 3The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui, 230001, People’s Republic of ChinaCorrespondence: Tian-Ping ZhangThe First Affiliated Hospital of University of Science and Technology of China, 17 Lujiang Road, Hefei, Anhui, 230001, People’s Republic of ChinaEmail zhangtianping@ustc.edu.cnBackground: Reactive oxygen species (ROS) generated by NADPH oxidase has a pivotal role in the nonspecific innate immune response to invading microorganisms including M. tuberculosis (MTB). NCF2 and NOX2 were considered as important functional subunits of NADPH oxidase complex; hence, this study aimed to evaluate the NCF2, NOX2 mRNA expressions in PBMC of pulmonary tuberculosis (PTB) patients.Methods: A total of 79 PTB patients and 73 controls were included in our study. Quantitative real-time reverse transcription polymerase chain reaction (qRT-PCR) was used to measure the NCF2, NOX2 mRNA levels, and receiver operating characteristic (ROC) curve analysis was performed to assess the diagnostic value of NCF2, NOX2 in PTB patients.Results: When compared to controls, the NCF2, NOX2 mRNA levels were significantly increased in PBMC from PTB patients (P < 0.001). However, the NCF2, NOX2 mRNA levels were not associated with major clinical and laboratory data of PTB patients. Area under curve (AUC) of ROC curve analysis for NCF2 and NOX2 were 0.686 (95% CI: 0.601, 0.770) and 0.705 (95% CI: 0.623, 0.787), respectively.Conclusion: Altered NCF2, NOX2 mRNA levels in PTB patients implied that these genes might play roles in PTB, and their expression levels might be potential biomarkers for the diagnosis of PTB.Keywords: pulmonary tuberculosis, NADPH oxidase complex, NCF2, NOX2, peripheral blood mononuclear cells

Hong-Miao Li,1,2,&ast; Li-Jun Wang,2,&ast; Fei Tang,3 Hai-Feng Pan,1 Tian-Ping Zhang4 1Department of Epidemiology and Biostatistics, School of Public Health, Anhui Medical University, Hefei, People’s Republic of China; 2Department of Infectious Diseases, The First Affiliated Hospital of Anhui Medical University, Hefei, People’s Republic of China; 3Anhui Chest Hospital (Anhui Provincial TB Institute), Hefei, Anhui, People’s Republic of China; 4The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Tian-Ping Zhang, The First Affiliated Hospital of USTC, 17 Lujiang Road, Hefei, Anhui, 230001, People’s Republic of China, Email zhangtianping@ustc.edu.cn Hai-Feng Pan, School of Public Health, Anhui Medical University, Hefei, 230032, Anhui, People’s Republic of China, Email panhaifeng@ahmu.edu.cnBackground: Recent studies have shown that abnormal expression of lncRNA NEAT1 is associated with the progression of pulmonary tuberculosis (PTB). The aim of our study was to analyze the relationship between single nucleotide polymorphisms (SNPs) of NEAT1 gene and susceptibility to PTB.Methods: Four SNPs (rs2239895, rs3741384, rs3825071, rs512715) in NEAT1 gene were genotyped in 479 patients with PTB and 476 controls by improved multiple ligase detection reaction (iMLDR) in a Chinese population.Results: We found no significant differences in allele and genotype frequencies of NEAT1 gene rs2239895, rs3741384, rs3825071, rs512715 between PTB patients and controls (all P > 0.05). There was no statistically significant association between genotype frequency distribution of dominant model, as well as recessive model, and genetic susceptibility to PTB patients (all P > 0.05). The TT genotype, T allele frequencies of rs3825071 were significantly increased in sputum smear-positive PTB patients when compared to sputum smear-negative PTB patients (P = 0.010, P = 0.003, respectively). Haplotype analysis shown that NEAT1 haplotype frequency was not associated with PTB susceptibility.Conclusion: NEAT1 gene polymorphisms were not associated with the risk of PTB in Chinese population, and rs3825071 polymorphism might be related to sputum smear-positive in PTB patients.Keywords: long non-coding RNA, NEAT1, pulmonary tuberculosis, single nucleotide polymorphisms

Recent studies have shown that abnormal expression of lncRNA NEAT1 is associated with the progression of pulmonary tuberculosis (PTB). The aim of our study was to analyze the relationship between single nucleotide polymorphisms (SNPs) ofFour SNPs (rs2239895, rs3741384, rs3825071, rs512715) inWe found no significant differences in allele and genotype frequencies of

The aim of our study was to investigate the association of leptin (LEP) gene (rs11761556, rs12706832, rs2167270), leptin receptor (LEPR) gene (rs1137100, rs1137101, rs1805096) variants and pulmonary tuberculosis (PTB) susceptibility, as well as their several clinical manifestations, in a Chinese population.This study included a cohort of 489 PTB patients and 489 healthy controls, and six SNPs were genotyped by improved multiple ligase detection reaction (iMLDR).We found that there were no significant differences regarding the allele and genotype frequencies of LEP rs11761556, rs12706832, rs2167270, LEPR rs1137100, rs1137101, rs1805096 between PTB patients and healthy controls (all P 0.05), as well as the results of the dominant model and recessive model (all P 0.05). In the LEP gene, the rs11761556 AA genotype frequency was significantly associated with the development of fever and pulmonary infection in PTB patients (P = 0.035, P = 0.049). In addition, the relation between main haplotypes and PTB patients was also analyzed, but only haplotype CAG in LEP was significantly associated with PTB susceptibility (P = 0.012).LEP and LEPR heritable variation were not contribute to the pathogenesis of PTB in Chinese. While rs11761556 variant might associate with several clinical features of PTB.

Abnormal vitamin D metabolism is involved in the pathogenesis of rheumatoid arthritis (RA). In this study, we evaluated the association of single nucleotide polymorphisms (SNPs) and methylation levels in vitamin D metabolic pathway genes with RA susceptibility. Ten SNPs in vitamin D metabolic pathway genes (CYP2R1, CYP24A1, VDR, CYP27B1) were genotyped in 477 RA patients and 496 controls by improved multiple ligase detection reaction (iMLDR). The methylation levels of the promoter regions of these genes were detected in 122 RA patients and 123 controls using Illumina Hiseq platform. We found that the CYP2R1 rs1993116 GA genotype, CYP27B1 rs4646536 GA genotype, rs4646536 A allele frequencies were significantly increased in RA patients when compared to controls. The decreased risk of rs1993116, rs4646536 was found under the dominant mode in RA patients. However, no significant association was found between CYP2R1 rs7936142, rs12794714, CYP24A1 rs2762934, rs6068816, rs2296239, rs2296241, VDR rs11574129, rs3847987 polymorphism, and RA susceptibility. The VDR, CYP27B1 methylation levels in RA patients were significantly lower than those in controls, while CYP2R1, CYP24A1 methylation levels were not associated with RA. There were no statistical associations between CYP2R1, CYP24A1, VDR, CYP27B1 methylation levels and their respective genotype in RA patients. In addition, plasma 25OHD level in RA patients was significantly lower than that in healthy controls. In summary, our results showed that CYP2R1, CYP27B1 genetic variations were associated with the genetic background of RA, while altered VDR, CYP27B1 methylation levels were related to the risk of RA.

Background and Objectives: The 3’ repair exonuclease 1 (TREX1) gene is the major DNA-specific 3’–5 ’exonuclease of mammalian cells which reduces single- and double-stranded DNA (ssDNA and dsDNA) to prevent undue immune activation mediated by the nucleic acid. TREX1 is also a crucial suppressor of selfrecognition that protects the host from inappropriate autoimmune activations. It has been revealed that TREX1 function is necessary to prevent host DNA accumulating after cell death which could actuate an autoimmune response. In the manuscript, we will discuss in detail the latest advancement to study the role of TREX1 in autoimmune disease. Methods: As a pivotal cytoprotective, antioxidant, anti-apoptotic, immunosuppressive, as well as an antiinflammatory molecule, the functional mechanisms of TREX1 were multifactorial. In this review, we will briefly summarize the latest advancement in studying the role of TREX1 in autoimmune disease, and discuss its potential as a therapeutic target for these diseases. Results: Deficiency of TREX1 in human patients and murine models is characterized by systemic inflammation and the disorder of TREX1 functions drives inflammatory responses leading to autoimmune disease. Moreover, much more studies revealed that mutations in TREX1 have been associated with a range of autoimmune disorders. But it is also unclear whether the mutations of TREX1 play a causal role in the disease progression, and whether manipulation of TREX1 has a beneficial effect in the treatment of autoimmune diseases. Conclusion: Integration of functional TREX1 biology into autoimmune diseases may further deepen our understanding of the development and pathogenesis of autoimmune diseases and provide new clues and evidence for the treatment of autoimmune diseases.

Objective This study aimed to evaluate the association of single nucleotide polymorphisms (SNPs) of vitamin D metabolic pathway genes with susceptibility to pulmonary tuberculosis (PTB). Methods Nine hundred seventy-nine patients (490 PTB cases and 489 healthy controls) were included in this study. Seventeen SNPs of vitamin D metabolic pathway genes, including CYP24A1, CYP27A1, CYP27B1, CYP2R1, GC, and DHCR7, were genotyped with improved multiple ligase detection reaction (iMLDR). Results The GC rs3733359 GA, rs16847024 CT genotypes were significantly associated with the reduced risk of PTB, and the rs3733359 A, rs16847024 T alleles were also associated with the decreased PTB susceptibility. The GT genotype of GC rs4588 variant was significantly higher in patients with PTB when compared to controls. Moreover, the increased risk of rs3733359 and rs16847024 variants, and a decreased risk of rs4588, were found under the dominant mode among the PTB patients. However, there was no significant relationship of CYP24A1, CYP27A1, CYP27B1, CYP2R1, and DHCR7 polymorphisms with the risk of PTB. In CYP27A1, the rs17470271 T and rs933994 T alleles were significantly associated with leukopenia, drug resistance in the PTB patients, respectively. In GC gene, the rs7041 and rs3733359 variants were found to be associated with pulmonary infection, fever in the PTB patients, respectively. The increased frequency of rs16847024 TT genotype was found in the PTB patients with fever and drug-induced liver damage. DHCR7 rs12785878 TT genotype, and T allele frequencies were both significantly associated with pulmonary infection in the PTB patients. The haplotype analysis showed that CYP24A1 TACT, CYP2R1 GGCT, GGAT, GC AATG haplotypes were related to PTB susceptibility. Conclusion Our study suggested that GC SNPs were associated with the genetic background of PTB. CYP27A1, GC, and DHCR7 genetic variations might contribute to several clinical phenotypes of PTB in Chinese.

IntroductionThe vitamin D metabolic pathway has been shown to play a pivotal role in the pathogenesis of pulmonary tuberculosis (PTB), and vitamin D receptor (VDR) and CYP2R1 gene variation are known to affect vitamin D status. Hence, this study aimed to evaluate VDR and CYP2R1 mRNA expression in peripheral blood mononuclear cells (PBMCs) in PTB patients.Material and methodsWe measured VDR and CYP2R1 mRNA levels in 75 PTB patients and 63 healthy controls by quantitative real-time reverse transcription polymerase chain reaction (qRT-PCR). The associations of VDR and CYP2R1 mRNA levels with clinical characteristics and laboratory indexes of PTB patients were also examined in this study.ResultsCompared to healthy controls, the VDR mRNA level was significantly higher, and the CYP2R1 mRNA level was significantly lower in PBMCs from PTB patients (p = 0.047, p = 0.008, respectively). The CYP2R1 mRNA level in PTB patients with drug-resistant, unilateral tuberculosis foci was significantly higher than that in PTB patients without these clinical characteristics (p = 0.005, p = 0.048, respectively). In addition, our results demonstrated that the VDR mRNA expression level was positively correlated with erythrocyte sedimentation rate (ESR) (p = 0.045), while the CYP2R1 mRNA level was negatively correlated with ESR in PTB patients (p = 0.020).ConclusionsAltered VDR and CYP2R1 mRNA expression levels among PTB patients suggest their involvement in this disease.

Background In this study, we aimed to assess mRNA expressions of visfatin and lipocalin‐2 in peripheral blood mononuclear cells (PBMCs) from patients with pulmonary tuberculosis (PTB). Methods Overall, 79 PTB patients and 71 healthy controls were enrolled. In PBMCs, mRNA expressions of visfatin and lipocalin‐2 were detected using real‐time quantitative polymerase chain reaction (qRT‐PCR), and the diagnostic value of these adipokine mRNAs in PTB patients was calculated through receiver operating characteristic (ROC) analysis. Results In PBMCs from PTB patients, the visfatin mRNA level was significantly higher than in healthy controls (P, In this study, we found that the visfatin mRNA expression level in PBMCs from PTB patients was significantly higher than that in healthy controls (P

Background Recently, increasing studies have revealed that leptin is involved in the development of rheumatoid arthritis (RA). This study is aimed at exploring the association of leptin gene single nucleotide polymorphisms (SNPs) with susceptibility to RA in a Chinese population. Methods We recruited 600 RA patients and 600 healthy controls from a Chinese population and analyzed their three leptin SNPs (rs10244329, rs2071045, and rs2167270) using the improved Multiplex Ligase Detection Reaction (iMLDR) assays. The associations of these SNPs with clinical manifestations of RA were also analyzed. Enzyme-linked immunosorbent assay (ELISA) was performed for plasma leptin determination. Results No significant difference in either allele or genotype frequencies of these three SNPs between RA patients and healthy controls was observed (all P > 0.05). Association between the genotype effects of dominant, recessive models was also not found (all P > 0.05). No significant difference in plasma leptin levels was detected between RA patients and controls (P > 0.05). Conclusion Leptin gene (rs10244329, rs2071045, and rs2167270) polymorphisms are not associated with RA genetic susceptibility and its clinical features in the Chinese population.

Objective Recent studies have focused on the special roles of NADPH-oxidase in multiple autoimmune diseases. Nevertheless, the association of genetic variation in NADPH-oxidase genes with rheumatoid arthritis (RA) was not extensively studied in a Chinese population. We performed this study to examine the association of NCF2, NCF4, and CYBA gene polymorphisms with RA susceptibility in a Chinese population. Methods Six single nucleotide polymorphisms (SNPs) (NCF2 rs10911363, NCF4 rs1883112, rs4821544, rs729749, CYBA rs3794624, and rs4673) were genotyped in a cohort composed of 593 RA patients and 596 normal controls. Improved multiple ligase detection reaction (iMLDR) was used for genotyping. Results We observed that NCF4 rs4821544 CT genotype and C allele frequencies in RA patients were significantly decreased when compared to controls (CT vs. TT: P = 0.043; C vs. T: P = 0.031), and rs4821544 polymorphism was significantly associated with an increased RA risk under the dominant model (TT vs. CT+CC: P = 0.031). Our results also indicated that rs729749 CT genotype frequency was significantly lower in RA patients than that in controls (CT vs. CC: P = 0.033). Moreover, the rs729749 CT genotype frequency was also significantly decreased in RA patients in males (CT vs. CC: P = 0.024). No significant association between NCF2 and CYBA gene polymorphisms and RA susceptibility was observed. There were significant associations between rs4821544 TT genotype and T allele frequencies and anti-CCP in male RA patients. Conclusions In summary, NCF4 rs4821544 and rs729749 polymorphisms might contribute to RA susceptibility, while NCF2 and CYBA gene polymorphisms were not associated with RA susceptibility.

Purpose of the study Increasing numbers of studies show that interleukin (IL)-10 plays a key role in the pathogenesis of autoimmune diseases including rheumatoid arthritis (RA) and acts as an immunomodulatory cytokine. The purpose of the present study was to analyse the relationship between gene single nucleotide polymorphisms (SNPs) in the IL-10 gene and RA susceptibility. Study design We genotyped three SNPs (rs1800890, rs3024495, rs3024505) of the IL-10 gene in a Chinese population of 354 RA patients and 367 controls. Genotyping was conducted using TaqMan SNP genotyping assays. Plasma IL-10 levels were measured by ELISA. Results The A allele of the rs1800890 variant was significantly related to decreased risk for RA compared with the T allele (A vs T: OR 0.580, 95% CI 0.345 to 0.975, P=0.038). No significant association between the genotype distribution of these SNPs and RA susceptibility was detected. The genotype effect of the dominant model was also evaluated, but no statistical difference was found. Further analysis in RA patients demonstrated that none of these SNPs were associated with rheumatoid factor (RF) or anti-citrullinated protein antibody (anti-CCP). In addition, no significant differences in plasma IL-10 levels were observed among RA patients with different genotypes. Conclusions The IL-10 rs1800890 variant might contribute to RA susceptibility in the Chinese population. Replication studies in different ethnic groups are required to further examine the critical role of IL-10 gene variation in the pathogenesis of RA.

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 P 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.

Aim Studies investigating the association between HLA-DQB1 alleles and rheumatoid arthritis (RA) have reported conflicting results. The purpose of this study was to evaluate whether DQB1 alleles confer susceptibility to RA. Design A comprehensive literature search up to May 2016 was conducted to identify case-control studies on the association of HLA-DQB1 alleles with RA. Pooled ORs with 95% CIs were used to assess the strength of association. Setting The literature indicates that HLA-DQB1 is associated with susceptibility to RA. Main outcome measures Frequencies of HLA-DQB1 alleles and phenotype in RA patients and healthy controls. Results Fifteen studies with 1250 cases and 1621 controls were included in this meta-analysis. DQB1 alleles were associated with RA susceptibility. The frequencies of DQB1*06 were lower in RA (p-value for comparability=0.007, OR 0.726,95% CI 0.576 to 0.916; p=0.004, OR 0.611,95% CI 0.438 to 0.852). The frequencies of DQB1*02 were lower in RA (p=0.044, OR 0.731,95% CI 0.597 to 0.895). A higher frequency of DQB1*04 was observed in RA (p=0.023, OR 1.604,95% CI 1.067 to 2.410). Conclusions This meta-analysis demonstrates that DQB1*02 and DQB1*06 may be negatively associated with RA. Conversely, DQB1*04 may confer susceptibility to RA.

To explore the association of LEP and leptin receptor (LEPR) gene single‐nucleotide polymorphisms (SNPs) with susceptibility to systemic lupus erythematosus (SLE) in a Chinese population. Four LEP SNPs (rs11761556, rs12706832, rs2071045 and rs2167270) and nine LEPR SNPs (rs10749754, rs1137100, rs1137101, rs13306519, rs8179183, rs1805096, rs3790434, rs3806318 and rs7518632) were genotyped in a cohort of 633 patients with SLE and 559 healthy controls. Genotyping of SNPs was performed with improved multiple ligase detection reaction (iMLDR). No significant differences were detected for the distribution of allele and genotype frequencies of all 13 SNPs between patients with SLE and controls. The genotype effects of recessive, dominant and additive models were also analysed, but no significant evidence for association was detected. However, further analysis in patients with SLE showed that the TT genotype and T allele frequencies of the LEP rs2071045 polymorphism were nominally significantly higher in patients with pericarditis (P = 0.012, P = 0.011, respectively). In LEPR, the GA/AA genotype and A allele frequencies of the rs1137100 polymorphism were both nominally associated with photosensitivity in patients with SLE (P = 0.043, P = 0.018, respectively). Moreover, the genotype and allele distribution of rs3806318 were also nominally associated with photosensitivity in patients with SLE (P = 0.013, P = 0.008, respectively). No significant differences in serum leptin levels were observed in patients with SLE with different genotypes. In summary, LEP and LEPR SNPs are not associated with genetic susceptibility to SLE, but may contribute to some specific clinical phenotype of this disease; further studies are necessary to elucidate the exact role of LEP and LEPR genes in the pathogenesis of SLE.

Background. Recently, increasing studies have revealed that leptin is involved in the development of rheumatoid arthritis (RA). This study is aimed at exploring the association of leptin gene single nucleotide polymorphisms (SNPs) with susceptibility to RA in a Chinese population. Methods. We recruited 600 RA patients and 600 healthy controls from a Chinese population and analyzed their three leptin SNPs (rs10244329, rs2071045, and rs2167270) using the improved Multiplex Ligase Detection Reaction (iMLDR) assays. The associations of these SNPs with clinical manifestations of RA were also analyzed. Enzyme-linked immunosorbent assay (ELISA) was performed for plasma leptin determination. Results. No significant difference in either allele or genotype frequencies of these three SNPs between RA patients and healthy controls was observed (all P > 0.05 ). Association between the genotype effects of dominant, recessive models was also not found (all P > 0.05 ). No significant difference in plasma leptin levels was detected between RA patients and controls ( P > 0.05 ). Conclusion. Leptin gene (rs10244329, rs2071045, and rs2167270) polymorphisms are not associated with RA genetic susceptibility and its clinical features in the Chinese population.

Objective. Recent studies have focused on the special roles of NADPH-oxidase in multiple autoimmune diseases. Nevertheless, the association of genetic variation in NADPH-oxidase genes with rheumatoid arthritis (RA) was not extensively studied in a Chinese population. We performed this study to examine the association of NCF2, NCF4, and CYBA gene polymorphisms with RA susceptibility in a Chinese population. Methods. Six single nucleotide polymorphisms (SNPs) (NCF2 rs10911363, NCF4 rs1883112, rs4821544, rs729749, CYBA rs3794624, and rs4673) were genotyped in a cohort composed of 593 RA patients and 596 normal controls. Improved multiple ligase detection reaction (iMLDR) was used for genotyping. Results. We observed that NCF4 rs4821544 CT genotype and C allele frequencies in RA patients were significantly decreased when compared to controls (CT vs. TT: P = 0.043 ; C vs. T: P = 0.031 ), and rs4821544 polymorphism was significantly associated with an increased RA risk under the dominant model (TT vs. CT+CC: P = 0.031 ). Our results also indicated that rs729749 CT genotype frequency was significantly lower in RA patients than that in controls (CT vs. CC: P = 0.033 ). Moreover, the rs729749 CT genotype frequency was also significantly decreased in RA patients in males (CT vs. CC: P = 0.024 ). No significant association between NCF2 and CYBA gene polymorphisms and RA susceptibility was observed. There were significant associations between rs4821544 TT genotype and T allele frequencies and anti-CCP in male RA patients. Conclusions. In summary, NCF4 rs4821544 and rs729749 polymorphisms might contribute to RA susceptibility, while NCF2 and CYBA gene polymorphisms were not associated with RA susceptibility.

Objective An increasing number of studies have demonstrated the roles of adipokines in systemic lupus erythematosus (SLE). We aimed to investigate the association of genetic variations of omentin-1, adiponectin, and resistin with SLE susceptibility. Methods We selected 623 SLE patients and 665 normal controls in the present study. Genotyping of omentin-1 rs2274907, rs35779394, rs79209815, and rs13376023; adiponectin rs16861194 and rs266729; and resistin rs1862513, rs3745368, and rs3745367 was conducted by TaqMan SNP genotyping assays. Results Overall, we found no significant differences in the allele or genotype frequencies of the nine studied SNPs between the SLE patients and controls. However, an increased frequency of the resistin rs3745368 variant was observed in the SLE patients under the dominant model (P = 0.024). In omentin-1, the rs13376023 A allele was found to be related to oral ulcers in SLE patients (P = 0.013), and the rs35779394 C and rs13376023 A allele frequencies were significantly lower in SLE patients with BMI ≥ 24 kg/m2 (P = 0.019, P = 0.033, respectively). For resistin, the frequencies of the rs3745368 AA genotype and A allele were lower in SLE patients with discoid rash (P = 0.036, P = 0.011), and the rs3745368 A allele frequency was higher in SLE patients with lupus nephritis (P = 0.018). The resistin rs3745367 AA genotype and A allele frequencies were related to the occurrence of renal disorder in SLE patients (P = 0.024, P = 0.009). The haplotype analysis showed that the CGA haplotype of resistin was associated with susceptibility to SLE (P = 0.005). No significant associations of plasma omentin-1, adiponectin or resistin levels with their respective genotypes were found in SLE patients. Conclusions In summary, omentin-1, adiponectin and resistin SNPs are not associated with the genetic background of SLE in Chinese patients. However, omentin-1 and resistin genetic variations might contribute to several clinical phenotypes of SLE.

Objective To evaluate the plasma levels of six adipokines, including chemerin, omentin-1, lipocalin-2, cathepsin-S, cathepsin-L and adipsin, in patients with SLE. Methods Ninety SLE patients and ninety control subjects were recruited, plasma adipokines levels were measured by enzyme-linked immunosorbent assay, and their associations with major clinical and laboratory indexes were analyzed. Results There were no significant differences in plasma chemerin, omentin-1, lipocalin-2, cathepsin-S, cathepsin-L and adipsin levels between SLE patients and controls. Further subgroup analyses by major clinical and laboratory indexes showed that plasma omentin-1 level was significantly lower in SLE patients without nephritis when compared with those patients with nephritis ( P = 0.002). Plasma chemerin, cathepsin-S levels in SLE patients without nervous system disorder were significantly lower in comparison with SLE patients with nervous system disorder ( P = 0.035, P = 0.029). No significant associations of other adipokines with any major clinical and laboratory indexes were observed. Conclusions Plasma levels of chemerin, omentin-1, lipocalin-2, cathepsin-S, cathepsin-L and adipsin in SLE patients were not markedly different from the normal controls. The presence of nephritis was connected with higher plasma omentin-1 levels in SLE patients, and the presence of nervous system disorder was associated with higher plasma chemerin, cathepsin-S levels in SLE patients. However, functional studies are awaited to further explore the potential roles of these cytokines in SLE.

Systemic lupus erythematosus (SLE) is a chronic autoimmune disorder characterized by multisystem organ involvement and unclear pathogenesis. Several adipokines synthesized in the adipose tissue, including leptin, adiponectin, resistin, and chemerin, have been explored in autoimmune rheumatic diseases, especially SLE, and results suggest that these mediators may be implicated in the pathogenesis of SLE. However, the current results are controversial. In this review, we will briefly discuss the expression and possible pathogenic role of several important adipokines, including leptin, adiponectin, resistin, and chemerin in SLE.

Background:Recent studies have focused on the special roles of NADPH-oxidase, which is composed of gp91phox, p22phox, p47phox, p67phox, p40phox encoded byCYBB,CYBA,NCF1,NCF2,NCF4genes, in multiple autoimmune diseases. Nevertheless, the association of genetic variation in NADPH-oxidase genes with rheumatoid arthritis (RA) was not extensively studied in Chinese population.Objectives:We performed this study to examine the association ofNCF2,NCF4,CYBAgenes polymorphisms with RA susceptibility in a Chinese population.Methods:Six single nucleotide polymorphisms (SNPs) (NCF2rs10911363,NCF4rs1883112, rs4821544, rs729749,CYBArs3794624, rs4673) were genotyped in a cohort composed of 593 RA patients and 596 normal controls. All patients were consecutively enrolled from the Department of Rheumatology at the First Affiliated Hospital of University of Science and Technology of China and the First Affiliated Hospital of Anhui Medical University, and the normal controls was enrolled from the same region. Improved multiple ligase detection reaction (iMLDR) was used for genotyping. Chi-square (χ2) test was used to analyze the association of the genotype and allele frequencies of above SNPs and RA. Odds ratios (OR) and 95% confidence interval (CI) were also evaluated using Logistic regression analyses, and haplotype analysis was assessed using SHEsis software.Results:There were 101 males and 492 females in RA group with a mean age of 51.59±6.68 years, and the normal control group included 97 males and 499 females with an average age of 52.32±12.63 years. We observed thatNCF4rs4821544 CT genotype, C allele frequencies in RA patients were significantly decreased when compared to controls (CT vs. TT:P= 0.043; C vs. T:P= 0.031), and rs4821544 polymorphism was significantly associated with an increased RA risk under the dominant model (TT vs. CT+CC:P= 0.031). Moreover, our results also indicated that rs729749 CT genotype frequency was significantly lower in RA patients than that in controls (CT vs. CC:P= 0.033). No significant association betweenNCF2,CYBAgenes polymorphisms and RA susceptibility was observed. There were no significant differences in allele, genotype frequencies of above SNPs between RA patients with RF-positive and with RF-negative, as well as anti-CCP-positive RA patients and anti-CCP-negative RA patients.Conclusion:In summary,NCF4rs4821544, rs729749 polymorphisms might contribute to RA susceptibility, whileNCF2,CYBAgenes polymorphisms were not associated with RA susceptibility.References:[1]Nauseef WM. Assembly of the phagocyte NADPH oxidase, Histochem Cell Biol, 2004;122:277-291.[2]Groemping Y, Rittinger K. Activation and assembly of the NADPH oxidase: a structural perspective, Biochem J (2005) 386:401-416.[3]Olsson LM, Nerstedt A, Lindqvist AK, Johansson SC, Medstrand P, Olofsson P, et al. Copy Number Variation of the Gene NCF1 Is Associated with Rheumatoid Arthritis, Antioxid Redox Signal(2012)16:71-78.DOI:10.1089/ars.2011.4013Table 1.Genotype and allele frequencies ofNCF2, NCF4, CYBAgenes polymorphisms in RA patients and controls [n(%)]SNPAnalyze modelRA (N = 593)Control (N = 596)P valueNCF2rs10911363GenetypesGG1251440.371GT3042890.747TT164163AllelesG5545770.408T632615NCF4rs1883112GenetypesGG57560.972GA2482550.754AA288285AllelesG3623670.888A824825rs4821544GenetypesCC470.323CT1171460.043TT472443AllelesC1251600.031T10611032Dominant modelTT4724430.031CT+CC121153rs729749GenetypesTT1041020.445CT2663020.033CC223192AllelesT4745060.219C712686CYBArs3794624GenetypesAA14150.929GA1601470.368GG41943AllelesA1881770.498G9981015rs4673GenetypesAA150.140GA85900.673GG507501AllelesA871000.34G10991092Acknowledgments:noDisclosure of Interests:None declared

Objective: To identify accurate occurrence and risk of cardiovascular (CV) events (stroke and myocardial infarction [MI]) in patients with systemic lupus erythematosus (SLE). Methods: Systemic literature search in PubMed and additional manual search were performed to obtain interested studies until March 31, 2018. The pooled incidences and risk of stroke and MI were calculated. Results: A total of 24 studies were included in this meta-analysis. For MI, a total of 1,516 SLE patients were reported to had MI (n = 96,154) over a mean follow-up of 9.98 years: incidence 2.0% (95% CI: 1.7–2.4%), i.e. 0.20/100 pyrs; in the five studies, 360 SLE patients (n = 18,943) and 817 controls had MI (n = 111,525), revealing that the risk of MI in SLE population was 3.04 times higher than in the general population (RR = 3.04, 95% CI: 1.81–5.11). For stroke, the incidence of 17 studies during the 10.09 follow-up period using random model was 4.4% (95% CI: 3.6–5.1%), i.e. 0.44/100 pyrs; in the 7 studies, 694 SLE patients (n = 22,594) and 4,034 controls had stroke (n = 255,023), indicating that the risk of MI in SLE population was 1.95 times higher than that in the general population (RR = 1.95, 95% CI: 1.52–2.53). Conclusion: Based on the findings from previous reports, our meta-analysis showed that patients with SLE have been at higher risk of CV events.

Purpose To explore the association of adiponectin (AD) and adiponectin receptor (ADR) gene single-nucleotide polymorphisms (SNPs) with genetic susceptibility to rheumatoid arthritis (RA) in a Chinese population. Study design Five AD SNPs (rs266729, rs2241766, rs1063537, rs2082940 and rs1063539) and two ADR SNPs (rs7539542 and rs12342) were genotyped in a cohort of 617 patients with RA and 639 healthy controls. Seven SNPs were genotyped using TaqMan genotyping assays on the Fluidigm 192.24 system. The concentration of AD in plasma was examined by ELISA. Results Patients with RA showed a considerably lower plasma level of AD than healthy controls (p=0.002). No significant differences were observed for the distribution of allele and genotype frequencies of rs266729, rs2241766, rs2082940, rs1063539, rs7539542 and rs12342 SNPs between patients with RA and controls. The genotype effects of recessive and dominant models were also analysed, but no marked evidence for association was found. However, further analysis in female patients with RA showed that the frequency of the AD gene rs1063539 GG genotype was nominally significantly higher in patients who were anti-cyclic citrullinated peptide (anti-CCP) antibody-positive (p=0.040). No significant differences in serum AD level were observed in patients with RA with different genotypes. Conclusions rs266729, rs2241766, rs2082940 and rs1063539 in the AD gene and rs7539542 and rs12342 in the ADR gene are possibly not associated with genetic susceptibility to RA, but the AD gene rs1063539 locus was possibly associated with anti-CCP in RA female patients.

Conclusion: Patients with RA have lower circulating IGF-1 level than healthy controls, particularly for patients from Asia and Europe. Further studies are necessary to elucidate the role of IGF-1 in the pathological process of RA. Results: A total of eleven articles with 334 cases and 261 controls were finally included. Compared with the healthy group, the RA group had lower circulating IGF-1 levels (pooled SMD= -0.936, 95% CI= -1.382 to -0.489, p Methods: PubMed, Embase and the Cochrane Library databases were searched up to December 2018 in English, and the studies comparing serum/plasma IGF-1 levels between RA group and healthy control group were what we are interested in. The Newcastle-Ottawa Scale (NOS) was used to assess the methodological quality of the included studies. The heterogeneity test was performed by the Cochrane Q statistic and I2 –statistic. The publication bias was evaluated by the funnel plot and Egger’s test. The standard mean difference (SMD) with 95% confidence interval (CI) was calculated by the fixed-effects or random-effects model. Background and Objectives: Insulin-like growth factor-1 (IGF-1) levels have been investigated in rheumatoid arthritis (RA), however, produced inconsistent results. The purpose of this meta-analysis was to derive a more precise conclusion about serum/plasma IGF-1 levels in RA patients.

Increasing studies have indicated the association between adipokines and multiple autoimmune diseases. This study aimed to evaluate the mRNA expression levels of vaspin, adiponectin and adrenomedullin in peripheral blood mononuclear cells (PBMCs) of patients with systemic lupus erythematosus (SLE), as well as their clinical associations.A total of 46 SLE patients and 51 normal controls were recruited. The three adipokines expression levels in PBMCs from SLE patients were measured by qRT-PCR, and their associations with major clinical and laboratory parameters of SLE patients were also analysed.Compared with normal controls, vaspin expression level in PBMCs was significantly decreased (p0.001), whereas adiponectin expression level was significantly higher in SLE patients (p0.001). There was no significant difference in adrenomedullin expression level between SLE patients and normal controls. Vaspin and adrenomedullin expression levels in more active SLE were significantly lower than those in less active SLE (p=0.012, p=0.046, respectively). No significant difference in these adipokine expression levels was observed between SLE patients with and without lupus nephritis (LN). There was also no significant association between mRNA levels of these adipokines and major clinical and laboratory parameters.Altered vaspin, adiponectin expression levels, and the associations between vaspin, adrenomedullin levels and disease activity in SLE patients suggested that these adipokines might play a role in SLE.

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

Currently published data regarding the relationship between plasma/serum leptin levels and systemic lupus erythematosus (SLE) are contradictory. To derive a more precise evaluation of this relationship, a meta-analysis was performed.Published literature from PubMed, Embase and Cochrane Library were obtained. The study quality was assessed by the Newcastle-Ottawa scale. Pooled standard mean difference (SMD) with 95% confidence interval (CI) was calculated by fixed-effects or random-effect model analysis. Heterogeneity among studies was estimated using the Cochran Q and I(2) statistics.A total of 11 studies including 868 SLE patients and 591 controls were finally included in the meta-analysis. No significant differences in plasma/serum leptin levels was found between SLE patients and healthy controls when all studies were pooled into the meta-analysis (pooled SMD = 0.269, 95% CI = -0.188 to 0.726). However, subgroup analyses showed that SLE patients from an Asian population, age ≥40 years and BMI25 had higher plasma/serum leptin levels when compared with controls.There is no significant difference in plasma/serum leptin levels between the entire group of SLE patients and controls. However, plasma/serum leptin levels are significantly higher in the subgroup of SLE patients from an Asian population ≥40 years of age and with a BMI25.

Increasing numbers of studies show that interleukin (IL)-10 plays a key role in the pathogenesis of autoimmune diseases including rheumatoid arthritis (RA) and acts as an immunomodulatory cytokine. The purpose of the present study was to analyse the relationship between gene single nucleotide polymorphisms (SNPs) in theWe genotyped three SNPs (rs1800890, rs3024495, rs3024505) of theThe A allele of the rs1800890 variant was significantly related to decreased risk for RA compared with the T allele (A vs T: OR 0.580, 95% CI 0.345 to 0.975, P=0.038). No significant association between the genotype distribution of these SNPs and RA susceptibility was detected. The genotype effect of the dominant model was also evaluated, but no statistical difference was found. Further analysis in RA patients demonstrated that none of these SNPs were associated with rheumatoid factor (RF) or anti-citrullinated protein antibody (anti-CCP). In addition, no significant differences in plasma IL-10 levels were observed among RA patients with different genotypes.The

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.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.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).The aberrant lncRNA expression levels and their associations with laboratory features in SLE suggest their important role in SLE pathogenesis.

The aim of this study was to investigate the association of interleukin (IL)-10 gene single nucleotide polymorphisms (SNPs) with susceptibility to systemic lupus erythematosus (SLE) in a Chinese population. 848 SLE patients and 461 normal controls were recruited in this study. Nine SNPs in IL-10 gene (rs1518110, rs1518111, rs1554286, rs1800890, rs1800893, rs3024493, rs3024495, rs3024498 and rs6667202) were genotyped using TaqMan genotyping assays on Fluidigm 192.24 system. The frequency of IL-10 rs3024498-C allele was significantly higher in patient group compared with control subjects (OR=5.118, 95% CI=1.819-14.405, P=0.002). No significant differences were detected for the distribution of allele and genotype frequencies of other eight SNPs between patients with SLE and controls after Bonferroni correction (all P>0.0056). Interestingly, significant differences were detected both in the allele and genotype frequencies of rs3024498 between SLE patients with and without arthritis (P=0.002, P=0.022, respectively).There was significant difference in genotype frequency at rs3024498 between SLE patients with and without malar rash (P=0.040). And, there was significant difference in allele frequency at rs3024498 between SLE patients with and without anti-double-stranded DNA (P=0.032). Meanwhile, significant difference in genotype frequency at rs1518110 and rs1518111 were found in patients with and without lupus headache (P=0.025, P=0.038, respectively). There were significant difference in allele and genotype frequency at rs1800890 and rs6667202 between SLE patients with and without thrombocytopenia (rs1800890: P=0.016, P=0.026, respectively; rs6667202: P=0.007, P=0.007, respectively). Further, significant difference were observed both in allele frequency and in genotype distribution of rs1800893 between patients with and without tubular urine and proteinuria (tubular urine: P