Ethnicity-stratified analysis of the association between IL-18 polymorphisms and systemic lupus erythematosus in a European population: a meta-analysis.

We performed a meta-analysis to identify the association between polymorphisms in the promoter of interleukin-18 (IL-18) and susceptibility for systemic lupus erythematosus (SLE) . Genotype data for three single-nucleotide polymorphisms (SNPs rs360719, rs1946518, and rs187238) in the IL-18 promoter were extracted from 20 studies of three different ethnicities (European, Asian, and South American). Data from each ethnicity group and their combinations were analyzed. We found distinct evidence of an association between rs360719 and SLE (P = 0.001) in the European/South American group [odds ratio (OR) 1.31 per C allele, 95% confidence interval (CI) 1.11-1.53]. Stratification analysis by ethnicity showed a significant association between rs360719 and SLE in the European population (OR 1.33 per C allele, 95% CI 1.11-1.61, P = 0.003) and a lesser effect in the same direction in the South American population (OR 1.18). A significant association was also identified between rs1946518 and SLE in the European population (OR 1.16 per A allele, 95% CI 1.03-1.30, P = 0.017), although there was no association in the Asian or the combined European/Asian population. We also examined genome-wide association study (GWAS) data from an Asian subpopulation (Chinese) for the association between rs1946518 and SLE, but found no association (P = 0.83). The third SNP, rs187238, was not significantly associated with SLE in any of the populations examined. In summary, this study identified a significant association between SLE and two SNPs within the IL-18 gene promoter region (rs360719 and rs1946518) in a European population, but not in populations of Asian origin.

CSE/H2S system protects mesenchymal stem cells from hypoxia and serum deprivation­induced apoptosis via mitochondrial injury, endoplasmic reticulum stress and PI3K/Akt activation pathways.

Mesenchymal stem cells (MSCs) have the potential to facilitate cardiac repair following acute myocardial infarction. However, MSC therapy is limited by apoptosis of the stem cells following transplantation. Hydrogen sulfide (H2S) has recently been proposed as an endogenous mediator of cell apoptosis in various systems. The aim of the present study was to investigate the mechanism underlying the antiapoptotic effect of the endogenous cystathionine γ-lyase (CSE)/H2S system in MSCs cultivated in conditions of hypoxia and serum deprivation (H/SD). Western blotting was performed in order to determine the expression of proteins associated with the mitochondrial injury pathway, endoplasmic reticulum stress and the phosphatidylinositol 3-kinase (PI3K)/Akt signaling pathway. It was demonstrated that H/SD is able to significantly induce apoptosis in MSCs. CSE overexpression, which enhances the endogenous H2S level, protects MSCs from H/SD-induced apoptosis via attenuation of the mitochondrial injury pathway, inhibition of endoplasmic reticulum stress and activation of the PI3K/Akt signaling pathway. In conclusion, the present findings suggest that modulation of the CSE/H2S system may a therapeutic approach with which to promote the viability of transplanted MSCs.

Association between C-reactive protein gene +1059 G/C polymorphism and the risk of coronary heart disease: a meta-analysis.

BACKGROUND: C-reactive protein (CRP) gene +1059 G/C polymorphism has been reported to be associated with coronary heart disease (CHD) risk, but the results remain inconclusive. This meta-analysis was therefore conducted to clarify these controversies. METHODS: A comprehensive search was conducted to identify all case control studies on the association between CRP gene +1059 G/C polymorphism and CHD risk. All the related studies were further strictly selected according to the inclusion criteria. Meta-analysis was performed with STATA 10.1 (StataCorp, USA). The association was assessed by odds ratio (OR) and 95% confidence interval (CI); both Begg's funnel plot and Egger's regression test were used to assess the publication bias. RESULTS: This meta-analysis on a total of 13 studies comprising 6316 CHD cases and 4467 controls showed no significant association between CRP gene +1059 G/C polymorphism and CHD risk in the overall study (for C/C+C/G vs. G/G: OR = 1.01, 95% CI = 0.81-1.25, P = 0.96; for C/C vs. C/G+G/G: OR = 1.17, 95% CI = 0.77-1.77, P = 0.47; for C/C vs. G/G: OR = 1.17, 95% CI = 0.77-1.77, P = 0.47; for C allele vs. G allele: OR = 1.01, 95% CI = 0.81-1.24, P = 0.96). However, in the subgroup analysis by ethnicity, the results showed significant association between CRP gene +1059 G/C polymorphism and CHD risk among Caucasians (for C/C vs. G/G: OR = 2.54, 95% CI = 1.13-5.72, P = 0.02; C/C vs. C/G+G/G: OR = 2.45, 95% CI = 1.09-5.51, P = 0.03), but not among Asians and Africans (P > 0.05). CONCLUSION: CRP gene +1059 G/C polymorphism may be associated with increased CHD risk among Caucasians and more evidences need to validate the conclusion.

Identification of B-cell epitopes in urease B subunit of Helicobacter pylori bound by neutralizing antibodies.

To identify linear B-cell epitopes of urease B (UreB), a series of 19 partially overlapping fragments of the UreB gene were expressed. Three MAbs against UreB of Helicobacter pylori (H. pylori), A1H10, A3C10, and B3D9, were tested for their reactivity to the truncated proteins by Western blot and enzyme-linked immunosorbent assay (ELISA). Three linear B-cell epitopes were identified covering a stretch of 15 amino acid (aa) residues and localized in the aa regions 158-172, 181-195, and 349-363 of UreB. ELISA also showed that the three synthetic peptides containing epitope sequences (UP32: GGGTGPADGTNATTI, UP35: WMLRAAEEYSMNLGF, and UP38: TLHDMGIFSITSSDS) were recognized by the corresponding MAbs and H. pylori positive sera from H. pylori infected patients. Mice immunized with glutathione S-transferase (GST) fusion peptides showed that epitope-specific antibodies were capable of inhibiting urease enzymatic activity. These results should be useful in clinical applications and highlight the potential importance of these epitopes as the targets for development of epitope-based vaccines against H. pylori.