H19 Increases IL-17A/IL-23 Releases via Regulating VDR by Interacting with miR675-5p/miR22-5p in Ankylosing Spondylitis.

Long non-coding RNA (lncRNA) H19 is associated with inflammatory diseases, but the molecular mechanism of H19 in the inflammatory process of ankylosing spondylitis (AS) is unclear. Here, we investigated the role of H19 and its downstream molecules in the inflammation of AS by microarray analysis, qRT-PCR, western blot, and dual-luciferase reporter assay. H19 small interfering RNA (siRNA) (Si-H19) and adenovirus (AD-H19) were used to decrease and increase H19 expression, respectively. 42 annotated lncRNAs were identified, and H19 was overexpressed. H19, vitamin D receptor (VDR), and transforming growth factor ß (TGF-ß) can bind to microRNA22-5p (miR22-5p) and miR675-5p. Si-H19 significantly downregulated miR22-5p and upregulated miR675-5p expression; Si-H19 decreased the protein and mRNA expression of VDR and decreased the cytokine and mRNA levels of interleukin-17A (IL-17A) and IL-23. These results were verified by AD-H19. In addition, miR22-5p and miR675-5p inhibitors increased the protein and mRNA expression of VDR and increased the cytokine and mRNA levels of IL-17A and IL-23. These results were also confirmed by miRNA mimics. Furthermore, H19 directly interfered with miR22-5p and miR675-5p expression, whereas the two miRNAs directly inhibited VDR expression. Overall, the H19-miR22-5p/miR675-5p-VDR-IL-17A/IL-23 signaling pathways have important roles in the pathogenesis of AS.

TNFAIP3 genetic polymorphisms reduce ankylosing spondylitis risk in Eastern Chinese Han population.

This study was conducted to clarify the associations of tumor necrosis factor-α induced protein 3 (TNFAIP3) and TNFAIP3-interacting protein 1 (TNIP1) genetic polymorphisms with ankylosing spondylitis (AS) susceptibility. Five single nucleotide polymorphisms (SNPs) in TNFAIP3 gene and four in TNIP1 gene were genotyped in 667 AS patients and 667 matched healthy controls. Genotypes and haplotype analysis were conducted by using SPSS 23.0 and Haploview 4.2 software. The T allele and CT genotype in TNFAIP3 rs10499194 were significantly associated with a reduced AS risk (T allele vs. C allele, OR = 0.619, 95% CI = 0.430-0.889, P = 0.009; CT vs. CC, OR = 0.603, 95% CI = 0.416-0.875, P = 0.007). However, no association remained significant after Bonferroni correction. The rs13207033A- rs10499194T haplotype of TNFAIP3 conferred a protective effect on AS susceptibility. Stratification analyses suggested that rs10499194 polymorphism decreased the risk of AS in the male subgroup, subgroup aged ≥ 29, HLA-B27 positive subgroup as well as the subgroups of BASFI < 4 and BASDAI < 4 (all P < 0.05). Furthermore, the functional annotation suggested a potential function of rs10499194 mutation. Our results demonstrated that TNFAIP3 rs10499194 polymorphism may be associated with a reduced risk of AS.

Chronic obstructive pulmonary disease in rheumatoid arthritis: a systematic review and meta-analysis.

BACKGROUND: The risk and prevalence of chronic obstructive pulmonary disease (COPD) in rheumatoid arthritis (RA) is still obscure. The current study was aimed to systematically review and meta-analyse the risk ratio (RR) and prevalence of COPD in RA. METHODS: A comprehensive systematic review was conducted based on PubMed, Web of Science and Cochrane Library from inception to April 30, 2018. The primary outcome of our study was the RR of COPD in RA patients compared with controls, and secondary was the prevalence of COPD in RA patients. Pooled effect sizes were calculated according to fixed effect model or random effects model depending on heterogeneity. RESULTS: Six and eight studies reported the RR and prevalence of COPD in RA respectively. Compared with controls, RA patients have significant increased risk of incident COPD with pooled RR 1.82 (95% CI = 1.55 to 2.10, P <  0.001). The pooled prevalence of COPD in RA patients was 6.2% (95% CI = 4.1 to 8.3%). Meta-regression identified that publication year was an independent covariate negatively associated with the RR of COPD, and smoker proportion of RA population was also positively associated with the prevalence of COPD significantly in RA patients. CONCLUSIONS: The present meta-analysis has demonstrated the significant increased risk and high prevalence of COPD in RA patients. Patients with RA had better cease tobacco use and rheumatologists should pay attention to the monitoring of COPD for the prevention and control of COPD.

Elevated circulating IL-17 level is associated with inflammatory arthritis and disease activity: A meta-analysis.

OBJECTIVES: Previous studies found that the interleukin (IL)-17 level was elevated in inflammatory arthritis, but results were inconsistent. This meta-analysis aimed to investigate the association of IL-17 cytokine with osteoarthritis (OA), rheumatoid arthritis (RA), ankylosing spondylitis (AS) and psoriatic arthritis (PsA). METHODS: Relevant studies were searched using databases. Standardized mean difference (SMD) was calculated. Correlation coefficient was utilized to evaluate the relationship between IL-17 and disease activity of AS and RA. Subgroup analysis, sensitivity analysis and meta-regression were applied to explore the sources of heterogeneity. RESULTS: 83 records were enrolled. The IL-17 level was elevated in AS (SMD = 2.348, P < .001), RA (SMD = 1.502, P < .001), PsA (SMD = 1.710, P < .001) and OA (SMD = 1.192, P = .016), and similar results occurred in subgroup analysis. Furthermore, the IL-17 level was positively associated with disease activity of AS and RA. CONCLUSION: Circulating IL-17 level is significantly elevated in inflammatory arthritis and is related to the disease activity of AS and RA, suggesting that it plays an important role in the pathogenesis and progression of inflammatory arthritis (especially in AS and RA).

Serum Levels of OPG, RANKL, and RANKL/OPG Ratio in Patients with Ankylosing Spondylitis: A Systematic Review and Meta-analysis.

Objectives: To investigate the role of osteoprotegerin (OPG), receptor activator of nuclear factor-kB ligand (RANKL), and RANKL/OPG ratio in the pathogenesis of ankylosing spondylitis (AS). Methods: Studies that compared serum levels of OPG, RANKL, and RANKL/OPG ratio between AS patients and healthy controls were gathered. Pooled standardized mean differences (SMDs) with 95% confidence intervals (CIs) were calculated by the random-effects model. Results: Twenty studies containing 1592 AS patients and 1064 healthy controls were included in this meta-analysis. Serum levels of OPG, RANKL, and RANKL/OPG ratio in AS patients were significantly higher than that in normal controls (OPG: SMD = 0.401, 95%CI = 0.026-0.777, p = 0.036; RANKL: SMD = 1.116, 95%CI = 0.510-1.723, p < 0.001; RANKL/OPG ratio: SMD = 0.691, 95%CI = 0.084-1.299, p = 0.026, respectively). Subgroup analysis suggested that Asian AS patients and patients with elevated ESR (ESR >20 mm/h) had higher serum OPG levels compared to normal controls. Asian patients, CRP >10 mg/L, ESR >20 mm/h, duration of disease ≤8 years, and BASDAI score >4 points subgroups showed increased RANKL levels compared to controls. Conclusions: Serum levels of OPG, RANKL, and RANKL/OPG ratio may be used as potential susceptible biomarkers for AS, but they could be influenced by race, inflammatory factors, and disease activity of AS patients.

The correlation between microRNA-221/222 cluster overexpression and malignancy: an updated meta-analysis including 2693 patients.

BACKGROUND: Although miR-221/222 cluster plays an important role in many human malignancies, the correlation between miR-221/222 cluster overexpression and tumor prognosis remains controversial. Therefore, an updated meta-analysis was conducted to clarify its prognostic value in malignancy. METHODS: We conducted a search of literature in English electronic databases of PubMed, Embase, and Cochrane Library, and Chinese electronic databases of China Biology Medicine disc and China National Knowledge Infrastructure to obtain appropriate studies. Besides, we extracted hazard ratios (HRs) and 95% CIs to evaluate the strength of the correlations. In addition, the results of different subgroups analyses and publication bias test were also shown in this article. RESULTS: 32 publications, including 15 tumor types and 2,693 patients were embraced in this meta-analysis. The results of univariate (HR =1.69, 95% CI: 1.18-2.44, P<0.01) and multivariate (HR =2.10, 95% CI: 1.63-2.69, P<0.01) analyses revealed that miR-221/222 cluster high expression in various tumors was significantly associated with adverse overall survival (OS). Correspondingly, we also found subgroups analyses consisted of country, miR-221/222 cluster component, sample size, and test method have similar results. CONCLUSION: miR-221/222 cluster overexpression was closely related to adverse OS in human carcinoma, while overexpression of miRNA-221/222 cluster could be viewed as a protection factor in prostate cancer. Blood-derived miR-221/222 cluster was not proper to assess OS.

Associations of Estrogen Receptor Alpha Gene Polymorphisms with Type 2 Diabetes Mellitus and Metabolic Syndrome: A Systematic Review and Meta-Analysis.

The associations between PvuII (T>C) and XbaI (A>G) polymorphisms of estrogen receptor alpha (ESR1) gene with type 2 diabetes mellitus (T2DM) or metabolic syndrome (MetS) are reported in many studies, but the results are inconsistent. This present work aims to assess the associations by performing a comprehensive meta-analysis. Relevant studies were searched through several databases. The pooled odd ratios (ORs) with 95% confidence intervals (CIs) were calculated to evaluate the associations of PvuII and XbaI polymorphisms with the risk of T2DM and MetS by using the STATA 14.0 software. Eight studies for T2DM and three articles about MetS were included in this meta-analysis. The overall results indicated that PvuII, rather than XbaI polymorphism, was associated with T2DM (regressive model: OR=0.673, 95% CI=0.550 to 0.823, praw<0.001, pFDR<0.003). The subgroup analysis based on race revealed an association of PvuII polymorphism with the decreased T2DM risk in Chinese population and a relationship between XbaI polymorphism and the reduced T2DM susceptibility in Caucasians. The difference of country may be one source of the heterogeneity for PvuII polymorphism and T2DM. However, neither PvuII nor XbaI polymorphism was related to the risk of MetS. The C allele of PvuII polymorphism presents a protective role in T2DM risk, especially in Chinese people. The G allele of XbaI polymorphism is related to a reduced risk for T2DM in Caucasian population. Nevertheless, neither of PvuII nor XbaI polymorphism is associated with MetS risk.

Serum levels of leptin, adiponectin and resistin in patients with ankylosing spondylitis: A systematic review and meta-analysis.

OBJECTIVES: Various studies have researched the serum levels of leptin, adiponectin and resistin in patients with ankylosing spondylitis (AS), but the results were inconclusive. The purpose of this study was to systematically evaluate the correlations between serum levels of these adipokines and AS. METHODS: Electronic databases were retrieved to search relevant publications. Pooled standard mean difference (SMD) with 95% confidence interval (CI) was calculated by the random-effect model. Cochrane Q test and I2 statistic were used to test heterogeneity. Subgroup analysis and meta-regression were applied to assess possible sources of heterogeneity. RESULTS: A total of sixteen articles were included. Meta-analysis results indicated no statistical differences between AS patients and normal controls in serum leptin and adiponectin levels (leptin, SMD=0.829, 95% CI=-0.116 to 1.774, p=0.085; adiponectin, SMD=0.460, 95% CI=-0.004 to 0.924, p=0.052). However, AS patients had higher serum resistin levels than controls (SMD=1.413, 95% CI=0.294 to 2.531, p=0.013). Subgroup analyses suggested that Asian and African AS patients as well as patients aged <40years had higher serum leptin and resistin levels when compared to controls. Serum adiponectin levels were higher in AS patients compared to controls in subgroup of age ≥40, and serum resistin levels in subgroup of BMI ≥25. Measurement method was a source of heterogeneity for resistin. Publication bias was not observed and the robustness of study results was confirmed by sensitivity analysis. CONCLUSION: Serum resistin, but not leptin or adiponectin levels may be closely associated with the development of AS.