Soluble Receptor for Advanced Glycation End Products (sRAGE) is Up-Regulated in Multiple Sclerosis Patients Treated with Interferon ß-1a.

BACKGROUND/AIMS: Multiple sclerosis (MS) is a chronic inflammatory disorder of the central nervous system. Considering the role of immune system in its pathogenesis, researchers have focused on evaluation of the expression of immune-related genes or proteins in MS patients. Among proteins whose participation in inflammatory process has been documented is the receptor for advanced glycation end products (RAGE). METHODS: In the present study, we compared RAGE transcript levels by means of quantitative real-time PCR as well as the serum level of soluble RAGE (sRAGE) by means of enzyme- linked immunosorbent assay (ELISA) in 50 IFNß-1a responsive relapsing-remitting MS patients when compared with age and sex-matched healthy subjects. RESULTS: Elevated expression of RAGE as well as higher levels of sRAGE were detected in IFN-ß responsive MS patients compared with the controls. A significant inverse correlation between sRAGE plasma concentrations and the expanded disability status scale (EDSS) was also detected in which each unit of increase in sRAGE level resulted in a 0.308 unit decrease in EDSS. CONCLUSION: Considering the stable clinical state of the MS patients in this study and their response to IFNß-1a, the elevated levels of sRAGE in patients compared with healthy subjects could be related to the effects of this kind of treatment.

The analysis of association between SNCA, HUSEYO and CSMD1 gene variants and Parkinson's disease in Iranian population.

Parkinson's disease (PD) is the second most prevalent neurodegenerative disorder. Both genetic and environmental factors are involved in the etiology of the disease. Many studies have revealed the susceptibility genes and variations for PD which need further confirmation. Here we evaluated the association of variations in SNCA, HUSEYO and CSMD1 genes with PD. A case-control study was conducted with 489 PD patients and 489 healthy controls. DNA was extracted from peripheral blood of all subjects and rs356220 and rs11931074 in SNCA, rs2338971 in HUSEYO and rs12681349 in CSMD1 were genotyped using PCR-RFLP method. The genotypes and allele frequencies were significantly different between case and control groups for rs356220, rs11931074 and rs2338971 but not for rs12681349. We provided further evidence that rs356220 is associated with increased risk of PD supporting previous studies in Caucasian-based and Japanese populations. The association of rs11931074 with decreased risk of PD was also significant. This study revealed the first evidence of the association of rs2338971 with increased risk of PD in the Iranian population. Nevertheless, these findings need further validation via more replication studies.

Association of Increased Levels of lncRNA H19 in PBMCs with Risk of Coronary Artery Disease.

OBJECTIVE: Considerable research shows that long non-coding RNAs, those longer than 200 nucleotides, are involved in several human diseases such as various cancers and cardiovascular diseases. Their significant role in regulating the function of endothelial cells, smooth muscle cells, macrophages, vascular inflammation, and metabolism indicates the possible effects of lncRNAs on the progression of atherosclerosis which is the most common underlying pathological process responsible for coronary artery disease (CAD). The aim of present study was to assess whether the expression of the lnc RNA H19 was associated with a susceptibility to CAD by evaluating the expression level of H19 in the peripheral blood. MATERIALS AND METHODS: A case-control study of 50 CAD patients and 50 age and sex-matched healthy controls was undertaken to investigate whether the H19 lncRNA expression level is associated with a CAD using Taqman Real-Time polymerase chain reaction (PCR). RESULTS: The subsequent result indicated that the H19 lncRNA was over-expressed in CAD patients in comparison with the controls. However, it was not statistically significant. This overexpression may be involved in coronary artery disease progression. CONCLUSION: We report here, the up-regulation of H19 lncRNA in the whole blood of CAD patients and suggest a possible role for H19 in the atherosclerosis process and its consideration as novel biomarker for CAD.

Association between Long Noncoding RNA ANRIL Expression Variants and Susceptibility to Coronary Artery Disease.

Animal cells possess thousands of long non-coding (lnc) RNAs, such as antisense noncoding RNA in the INK4 locus (ANRIL), which have regulatory roles in the cells' molecular mechanisms, including X-chromosome inactivation, and developmental processes. These lnc RNAs are known to influence the extensive spectrum of age-related disorders. Accordingly, there is evidence for the role of these lnc RNAs in cardiovascular diseases, particularly coronary artery diseases (CAD). The aim of this study was to assess whether the expression of the lnc RNA ANRIL was associated with a susceptibility to CAD by evaluating the expression level of the two transcripts of ANRIL. Peripheral blood was taken from fifty patients affected by CAD and relative expression of ANRIL was determined by Real-Time PCR assay. The obtained data indicated that the EU741058 transcript expression level significantly decreased in CAD patients in comparison with the healthy individuals (P= 0.001). Furthermore, there was no significant association between the NR_003529 transcript expression, and CAD risk in Iranian patients (P=0.751). Our results suggest that the expression level of the EU741058 transcript of ANRIL may be implicated in CAD development, creating a predictive biomarker for CAD patients in future.

Ecotropic Viral Integration Site 5 (EVI5) expression analysis in multiple sclerosis patients.

BACKGROUND: Multiple sclerosis (MS) is a complex immune-related disorder of the central nervous system (CNS) in which dysregulation of different classes of T cells are involved. Variants in Ecotropic Viral Integration Site 5 (EVI5) gene has been shown to be significantly associated with MS in different populations. OBJECTIVES: However, there is no data regarding relative expression of this gene in peripheral blood of MS patients compared with healthy controls. METHODS: In the present study we assessed expression of EVI5 in 50 Iranian MS patients compared with healthy subjects by means of quantitative real time RT-PCR. RESULTS: Statistical analyses showed no significant difference in EVI5 relative expression neither between total MS patients and healthy controls nor between age- and sex-based subgroups of patients and controls except for a trend toward significance in patients aged between 30 and 40 years compared with healthy subjects in both sexes (P= 0.068 and 0.075 for males and females respectively). No significant correlation was found between the expression level of this gene and disease duration, age at onset or Expanded Disability Status Scale (EDSS). CONCLUSION: Future studies are needed to explore the role of EVI5 in the pathogenesis of MS.

Expression Analysis of Long Non-coding RNAs in the Blood of Multiple Sclerosis Patients.

Multiple sclerosis (MS) is a chronic immune-mediated disorder of the central nervous system (CNS) with multiple genetic and environmental risk factors. Long non-coding RNAs (lncRNAs) have been recently reported to participate in the regulation of immune responses. Consequently, aberrant expression of lncRNAs has been suggested as an underlying cause of MS. In the present study, we evaluated the expression of three lncRNAs with putative roles in the regulation of immune response, namely TNF-α and heterogeneous nuclear ribonucleoprotein L (THRIL), Fas cell surface death receptor- antisense 1 (FAS-AS1), and plasmacytoma variant translocation 1 (PVT1) in circulating blood cells of 50 Iranian relapsing-remitting multiple sclerosis (RRMS) patients compared with healthy subjects by means of quantitative real-time polymerase chain reaction (PCR). We detected a significant downregulation of PVT1 and FAS-AS1 expressions in RRMS patients while a significant upregulation of THRIL in patients compared with controls (P < 0.001). Correlation analyses between lncRNA expression levels and clinical data of MS patients revealed no significant correlation between lncRNAs expression levels and Expanded Disability Status Scale (EDSS), a moderate correlation between PVT1 expression levels and duration of the disorder and no significant correlation between lncRNAs expression levels and age at onset. In addition, we demonstrated correlations between the expression levels of PVT1 and THRIL as well as expression levels of THRIL and FAS-AS1 in RRMS patients. In brief, we have demonstrated dysregulation of three lncRNAs in MS patients. Further studies are needed to explore the exact mechanisms by which these lncRNAs participate in regulation of immune responses.