A meta-analysis of the relationship between MYO9B gene polymorphisms and susceptibility to Crohn's disease and ulcerative colitis.

OBJECTIVE: Both Crohn's disease (CD) and ulcerative colitis (UC) have a complex etiology involving multiple genetic and environmental factors. Multiple UC and CD susceptibility genes have been identified through genome-wide association studies and subsequent meta-analyses. The aim of this meta-analysis was to clarify the impact of MYO9B gene polymorphisms on CD and UC risk. METHODS: The PubMed, Elsevier Science Direct and Embase databases were searched to identify eligible studies that were published before October 2014. Data were extracted and pooled crude odds ratios (ORs) and 95% confidence intervals (95% CIs) were calculated. RESULTS: A total of 11 studies, containing 3297 CD cases, 3903 UC cases and 8174 controls were included in this meta-analysis. Bonferroni correction results showed that rs1545620 A/C polymorphism of MYO9B gene was associated with both CD and UC susceptibility in Caucasians (OR=0.88, 95% CI=0.82∼0.95, P=0.001; OR=0.82, 95% CI=0.76∼0.89, P<0.001), but not in Chinese. rs1457092 G/T and rs2305764 C/T polymorphisms are associated with UC susceptibility (OR=0.85, 95% CI=0.79∼0.91, P<0.001; OR=0.88, 95% CI=0.83∼0.93, P<0.001), but not with CD susceptibility in Caucasians. CONCLUSIONS: This meta-analysis suggested that rs1545620 is both CD and UC susceptible locus in Caucasians; rs1457092 and rs2305764 are UC susceptible loci, but are not CD susceptible loci in Caucasians. Further studies with more sample size are needed for a definitive conclusion.

TCR-CD3ζ gene polymorphisms and expression profile in rheumatoid arthritis.

OBJECTIVES: Recent evidence has demonstrated that CD3ζ (also called CD247) play a vital role in multiple autoimmune diseases. In this study, we explored the association between CD247 gene single-nucleotide polymorphisms (SNPs) and rheumatoid arthritis (RA) in a Chinese Han population. We also evaluated the CD3ζ expression profile in peripheral blood mononuclear cells (PBMCs) from patients with RA and health controls. METHODS: Three CD247 polymorphisms (rs704853, rs1214611 and rs858554) were studied in 612 patients with RA and 848 controls in a Chinese population. Genotyping was performed using the Fluidigm 192.24 Dynamic Array™ Integrated Fluidic Circuit (IFC). For gene expression study, CD3ζ mRNA levels of 36 patients with RA and 39 healthy individuals were assessed by real-time polymerase chain reaction (RT-PCR). Data were analyzed by SPSS 11.5 software. RESULTS: A significant association between rs858554 polymorphism and RA was found under all genetic models (all p < 0.05). Moreover, we found the genotype distribution and allele frequency of rs858554 were significant associated with ACCP+ and RF+ phenotype as compare to health controls (all p < 0.05). Unfortunately, we did not detect any significant associations between rs704853, rs1214611 and RA susceptibility and autoantibody profiles (all p > 0.05). The gene expression assays showed that CD3ζ mRNA levels were downregulated in PBMCs of patients with RA when compared to healthy controls. CONCLUSIONS: Our results, the first reported for distinct Chinese populations, support a role of the CD247 gene in the susceptibility to RA. Further studies with more sample size are necessary to clarify the exact role of CD247 gene in the pathogenesis of RA.

Association Study of Matrix Metalloproteinases Gene Polymorphisms with Susceptibility to Rheumatoid Arthritis: A Meta-Analysis.

OBJECTIVE: Association of matrix metalloproteinases (MMPs) gene polymorphisms with rheumatoid arthritis is controversial. We conduct a meta-analysis to clarify this dispute. METHODS: We systematically searched the electronic PUBMED, EMBASE and CNKI databases for research articles about MMPs (MMP-1, MMP-2, MMP-3, MMP-9) gene polymorphisms and rheumatoid arthritis (RA) up to January 2015. According to the heterogeneity, fixed-effects or random-effects models were used to calculate crude odds ratios (ORs) and 95% confidence intervals (95% CIs). RESULTS: A total of 11 articles involving 2143 cases and 2049 controls were included in this meta-analysis. Overall, no significant associations were observed between MMP-1-1607 1G/2G polymorphism and RA. Stratification by ethnicity, no significant associations were observed in Caucasian populations. Similarly, no significant associations were observed between MMP-3-1171 5A/6A, MMP-9-1562 C/T polymorphisms and RA in overall and Caucasian populations, respectively. However, a weak association was found between MMP-2-1306 C/T polymorphism and RA (C vs. T, OR = 0.813, 95%CI = 0.694-0.953, p = 0.010) in overall populations. CONCLUSIONS: The present meta-analysis suggests that MMP-1-1607 1G/2G, MMP-3-1171 5A/6A, MMP-9-1562 C/T polymorphisms are not associated with the susceptibility of RA, but MMP-2 -1306 C/T is weakly associated with susceptibility to RA. Further studies with more sample size are needed for definitive conclusions.

Association of lymphotoxin alpha polymorphism with systemic lupus erythematosus and rheumatoid arthritis: a meta-analysis.

AIM: The aim of this study was to perform a meta-analysis of eligible studies to derive precise estimation of the associations of lymphotoxin alpha (LTA) 252 A>G polymorphism (rs909253) with systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA) risk. METHOD: Data were collected from the following electronic databases, including EMBASE, PubMed and China National Knowledge Infrastructure (CNKI). A total of 19 studies (13 studies involving 1346 SLE patients and 1951 controls, six studies involving 1079 RA patients and 1057 controls) were included. RESULTS: This meta-analysis showed no evidence of significant association of the A allele with SLE susceptibility (odds ratio [OR] 1.26; 95% confidence interval [CI] 0.98-1.62, P = 0.073), but it showed a weaker association under an additive model (OR 1.63, 95%CI 1.01-2.65, P = 0.047). Stratification by ethnicity indicated that the variant A allele carriers increased the risk of SLE in Asians (OR 1.91, 95%CI 1.44-2.53, P < 0.001). However, we failed to reveal any association between LTA gene 252 A>G polymorphism and RA risk under all models (for A vs. G: OR 1.02, 95%CI 0.79-1.33, P = 0.853; for AA + AG vs. GG: OR 0.86, 95%CI 0.52-1.41, P = 0.542; for AA vs. AG + GG: OR 1.19, 95%CI 0.80-1.78, P = 0.394, for AA vs. GG: OR 1.03, 95%CI 0.58-1.84, P = 0.919). Similar results were obtained in the subgroup analysis based on ethnicity. CONCLUSION: The present study suggests that LTA 252 A>G polymorphism is associated with SLE susceptibility in Asians, and there is no significant association between LTA 252 A>G polymorphism and RA.

Serum resistin levels in patients with rheumatoid arthritis and systemic lupus erythematosus: a meta-analysis.

The purpose of this meta-analysis was to investigate whether serum resistin level was associated with rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE) by comparing serum resistin levels between RA or SLE patients and normal controls. PubMed and EMBASE databases (up to May 13, 2014) were used to search all related articles. The weighted mean differences (WMDs) with 95 % confidence interval (CI) were calculated using random-effect model analysis. The Cochrane Q test and I(2) statistic were used to test heterogeneity. To assess publication bias, the Egger's test and visual observation of a funnel plot were used. The Newcastle-Ottawa scale was used to assess the study quality. The STATA statistical software (version 11.0) was applied to deal with statistical data. A total of eight studies of RA including 620 patients and 460 healthy controls, and six studies of SLE including 559 patients and 430 healthy controls were finally included in the meta-analysis. The results revealed that the serum resistin levels in RA were significantly higher than those in normal controls (WMD = 0.767 ng/ml, 95 % CI = 0.114-1.419, P = 0.021), but there was no significant difference between SLE patients and normal controls (WMD = 2.771 ng/ml, 95 % CI = -0.521-6.063, P = 0.099). Publication bias was undetected. In conclusion, this meta-analysis indicate that serum resistin level was significantly elevated in RA patients.

[Laser scanning confocal microscopic imaging for Ca2 + oscillations of pancreatic acinar cells in mice].

OBJECTIVE: To establish a simple but effective method of laser scanning confocal microscopic imaging for Ca2+ oscillations of pancreatic acinar cells in adult mice. METHODS: Pancreatic acinar cells from adult Kunming mice were isolated acutely with collagenase, and then loaded with fluo-4-AM, a Ca2+ indicator. A laser scanning confocal microscope armed with 488 nm laser was employed to record the dynamic fluorescent signals in-time and synchronously while acetylcholine (ACh) was added in the pancreatic acinar cells. RESULTS: (1) The classic pancreatic acinar cell Ca2+ oscillations were induced by a certain concentration of ACh (100 nmol/L) successfully and steadily, which could be blocked by atropine completely. (2) Plasmic Ca2+ oscillations from different parts of one acinar cell were usually with different amplitudes and almost the same frequencies. But both of amplitudes and frequencies were different among different cells. (3) The acinar cell Ca2+ oscillations were induced by ACh in a concentration-dependent manner. CONCLUSION: The laser scanning confocal microscopic imaging for adult mouse pancreatic acinar cell Ca2+ oscillations was established successfully. The features of being easy to use, direct to see lively, high efficiency and good flexibility make it a popular tool for researchers to choose.

Congo red modulates ACh-induced Ca(2+) oscillations in single pancreatic acinar cells of mice.

AIM: Congo red, a secondary diazo dye, is usually used as an indicator for the presence of amyloid fibrils. Recent studies show that congo red exerts neuroprotective effects in a variety of models of neurodegenerative diseases. However, its pharmacological profile remains unknown. In this study, we investigated the effects of congo red on ACh-induced Ca(2+) oscillations in mouse pancreatic acinar cells in vitro. METHODS: Acutely dissociated pancreatic acinar cells of mice were prepared. A U-tube drug application system was used to deliver drugs into the bath. Intracellular Ca(2+) oscillations were monitored by whole-cell recording of Ca(2+)-activated Cl(-) currents and by using confocal Ca(2+) imaging. For intracellular drug application, the drug was added in pipette solution and diffused into cell after the whole-cell configuration was established. RESULTS: Bath application of ACh (10 nmol/L) induced typical Ca(2+) oscillations in dissociated pancreatic acinar cells. Addition of congo red (1, 10, 100 µmol/L) dose-dependently enhanced Ach-induced Ca(2+) oscillations, but congo red alone did not induce any detectable response. Furthermore, this enhancement depended on the concentrations of ACh: congo red markedly enhanced the Ca(2+) oscillations induced by ACh (10-30 nmol/L), but did not alter the Ca(2+) oscillations induced by ACh (100-10000 nmol/L). Congo red also enhanced the Ca(2+) oscillations induced by bath application of IP3 (30 µmol/L). Intracellular application of congo red failed to alter ACh-induced Ca(2+) oscillations. CONCLUSION: Congo red significantly modulates intracellular Ca(2+) signaling in pancreatic acinar cells, and this pharmacological effect should be fully considered when developing congo red as a novel therapeutic drug.