Reduction of GAS5 and FOXD3-AS1 long non-coding RNAs in patients with bipolar disorder.

Bipolar disorder (BD) patients suffer from severe disability and premature death because of failure in prognosis, diagnosis, and treatment. Although neural mechanisms of bipolar have not been fully discovered, studies have shown long noncoding RNAs (lncRNAs) can play an important role in signaling pathways such as PI3K/AKT pathway. There has been little study on deregulated lncRNAs and the lncRNAs' mode of action in the BD. Hence, we aimed to investigate the expression of PI3K/AKT pathway-related lncRNAs named TUG1, GAS5, and FOXD3-AS1 lncRNAs in the PMBC in 50 bipolar patients and 50 healthy controls. Our results showed that FOXD3-AS1 and GAS5 under-expressed significantly in bipolar patients compared to healthy controls (P = 0.0028 and P < 0.0001 respectively). Moreover, after adjustment, all P values remained significant (q value < 0.0001). According to the ROC curve, AUC (area under the curve), specificity, and sensitivity of these lncRNAs, GAS5 and FOXD3-AS1 might work as BD candidate diagnostic biomarkers. Taken together, the current results highlight that the dysregulation of FOXD3-AS1 and GAS5 may be associated with an increased risk of BD.

The Emerging Roles of the ß-Secretase BACE1 and the Long Non-coding RNA BACE1-AS in Human Diseases: A Focus on Neurodegenerative Diseases and Cancer.

The ß-Secretase (BACE1) is widely studied to be particularly involved in amyloid deposition, a process known as the pathogenic pathway in neurodegenerative diseases. Therefore, BACE1 expression is frequently reported to be upregulated in brain samples of the patients with Alzheimer's disease (AD). BACE1 expression is regulated by BACE1-AS, a long non-coding RNA (lncRNA), which is transcribed in the opposite direction to its locus. BACE1-AS positively regulates the BACE1 expression, and their expression levels are regulated in physiological processes, such as brain and vascular homeostasis, although their roles in the regulation of amyloidogenic process have been studied further. BACE1-AS dysregulation is reported consistent with BACE1 in a number of human diseases, such as AD, Parkinson's disease (PD), heart failure (HF), and mild cognitive impairment. BACE1 or less BACE1-AS inhibition has shown therapeutic potentials particularly in decreasing manifestations of amyloid-linked neurodegenerative diseases. Here, we have reviewed the role of lncRNA BACE1 and BACE1-AS in a number of human diseases focusing on neurodegenerative disorders, particularly, AD.

The role of circular RNAs in pancreatic cancer: new players in tumorigenesis and potential biomarkers.

Circular RNAs (circRNAs) are a newly identified class of non-coding RNAs (ncRNAs) which show different structure compared to other RNAs in terms of their covalently closed ends. To date, a huge number of circRNAs have been identified in various species and also several databases have been created for storing and providing accessibility to retrieved data on identified circRNAs. They are produced by back-splicing from mainly protein-coding genes. Same to other ncRNAs, circRNAs have been found to play role in gene regulation via interaction with other biomolecules like nucleic acids, proteins and microRNAs (miRNAs). They are involved in different physiological processes like vascular functions, brain and embryonic development, regulation of metabolism, cell cycle control and response to cellular stress. Dysregulation of circRNAs have been associated with many types of human diseases like cardiovascular diseases, immune diseases, neurologic diseases, diabetes and particularly various types of cancer. In this review, we have a look to the cellular experiments conducted on the role of circRNAs in the pancreatic cancer. Two cellular behaviors of two categories of circRNAs including up-regulated and down-regulated transcripts have been reviewed in pancreatic cancer. Furthermore, their potential application in diagnosis and prognosis of pancreatic cancer has been summarized. The results show circRNAs are potential diagnostic and prognostic biomarkers of pancreatic cancer.

Phosphatidylinositol 3-kinase signaling inhibitors for treatment of multiple myeloma: From small molecules to microRNAs.

Multiple myeloma is one of the most hard-to-treat cancers among blood malignancies due to the high rate of drug resistance and relapse. The researchers are trying to find more effective drugs for treatment of the disease. Hence, the use of drugs targeting signaling pathways has become a powerful weapon. Overactivation of phosphatidylinositol 3-kinase signaling pathways is frequently observed in multiple myeloma cancer cells, which increases survival, proliferation, and even drug resistance in such cells. In recent years, drugs that inhibit the mediators involved in this biological pathway have shown promising results in the treatment of multiple myeloma. In the present study, we aimed to introduce phosphatidylinositol 3-kinase signaling inhibitors which include small molecules, herbal compounds, and microRNAs.

Circular RNAs in renal cell carcinoma: Functions in tumorigenesis and diagnostic and prognostic potentials.

Circular RNAs (circRNAs) are non-coding RNAs with closed ends which makes them resistant to degrading enzyme RNAse R. These RNA molecules show cell, tissue or organ specific expression. Regulatory functions have been reported for a number of circRNAs. Particularly, they have been found to affect cell cycle and control cell proliferation. CircRNAs are involved in physiological processes like natural organ development. Their dysregulation in high-throughput technologies have been shown in a growing number of diseases especially many types of cancers such as renal cell carcinoma (RCC). Differentially expressed circRNAs in RCC tissues compared to normal tissues may affect carcinogenesis process. Overexpressed circRNAs promote tumorigenic functions of RCC cell lines while down-regulated transcripts repress them. Both dysregulated circRNAs are correlated with clinicopathological features, prognosis and survival in RCC patients which along with their acceptable diagnostic values suggest them as potential biomarkers in diagnosis or prediction of prognosis of RCC patients. In this review, we have assessed tumorigenic or tumor-suppressing effects of circRNAs and also their diagnostic and prognostic potentials in RCC.

Identification of oxytocin-related lncRNAs and assessment of their expression in breast cancer.

Oxytocin is a neuropeptide released by the central nervous system. A number of studies have demonstrated the role of this neuropeptide in the pathogenesis of breast cancer. In the present project, we have identified mRNA coding genes and long non-coding RNAs (lncRNAs) that are associated with this pathway through an in-silico strategy, and measured their expression in a cohort of Iranian females affected with this type of malignancy. Expression levels of OXTR, FOS, ITPR1, RCAN1, CAMK2D, CACNA2D and lnc_ZFP161 were significantly down-regulated in breast cancer tissues compared with nearby non-cancerous tissues. On the other hand, expression of lnc_MTX2 was higher in breast cancer tissues compared with controls. Expression of lnc_TNS1 and lnc_FOXF1 were not different between these two kinds of samples. Expression of CACNA2D was associated with mitotic rate and PR status (P values = 3.02E-02 and 2.53E-02, respectively). Expression of other oxytocin-related genes was not associated with clinicopathological parameters. FOS and ITPR1 had the highest AUC value among the oxytocin-related genes. Combination of expression profiles of all oxytocin-related genes increased the AUC value to 0.75. However, the combinatorial sensitivity and specificity values were lower than some individual genes. In the breast cancer tissues, the most robust correlations have been detected between lnc_ZFP161/ lnc_FOXF1, CAMK2D/ lnc_ZFP161 and CAMK2D / lnc_FOXF1 (r = 0.86, 0.71 and 0.64 respectively). In the non-cancerous tissues, the strongest correlation was detected between lnc_FOXF1/lnc_MTX2 and lnc_ZFP161/CAMK2D respectively (r = 0.78 and 0.65). Taken together, oxytocin-associated genes have been dysregulated in breast cancer tissues. Moreover, the correlation ratio between these genes is connected with the existence of cancer.

Regulatory role of microRNAs on PTEN signaling.

Phosphatase and tensin homolog (PTEN) gene encodes a tumor suppressor protein which is altered in several malignancies. This protein is a negative regulator of the PI3K/AKT signaling. Several transcription factors regulate the expression of PTEN in positive or negative directions. Moreover, numerous microRNAs (miRNAs) have functional interactions with PTEN and inhibit its expression. Suppression of PTEN can attenuate the response of cancer cells to chemotherapeutic agents. Based on the critical role of this tumor suppressor gene, the identification of negative regulators of its expression has practical significance particularly in the prevention and management of cancer. Meanwhile, the interaction between miRNAs and PTEN has functional consequences in non-malignant disorders including myocardial infarction, osteoporosis, cerebral ischemic stroke, and recurrent abortion. In the present review, we describe the role of miRNAs in the regulation of expression and activity of PTEN.

Differential Expression of Cytokine-Coding Genes among Migraine Patients with and without Aura and Normal Subjects.

Migraine is a prevalent disorder in humans and represents one of the top 10 causes of years lived with disability. Several genetic and environmental factors are involved in the pathobiology of migraine. A number of studies have underscored the role of dysregulated immune reactions. We compared the expression levels IL-2, IL-4, CXCL8, IL-17, IFN-γ, TGF-ß and TNF-α cytokines in blood specimens of patients with migraine and those of healthy persons to identify any possible dysregulation in their expression and to propose mechanisms for this disorder. Expression of INF-γ was suggestively higher in migraine cases than in healthy individuals (posterior beta = 0.35, adjusted P value = 0.017). In addition, expression of this cytokine was lower in female subjects than in male subjects (posterior beta = -0.712, adjusted P value = 0.012). Expression of IL-4, TGF-ß and TNF-α was also higher in cases compared with controls (posterior beta = 1.34, adjusted P value = 0.04; posterior beta = 0.849, adjusted P value = 0.036; posterior beta = 0.451, adjusted P value = 0.042, respectively). On the other hand, CXCL8 expression was lower in migraine cases than in controls (posterior beta = -0.78, adjusted P value = 0.039). Expression levels of IL-1B, IL-17 and IL-2 were not meaningfully different between cases and controls. The current study highlights the dysregulation of cytokine-coding genes in the blood of patients with migraine.

The lncRNA ANRIL is down-regulated in peripheral blood of patients with periodontitis.

Long non-coding RNAs (lncRNAs) have crucial roles in lncRNAs in periodontal development and disorders of this tissue. A number of lncRNAs especially those regulating immune responses contribute in the pathophysiology of periodontitis. In the current case-control study, we assessed expression levels of two immune response-related lncRNAs namely the antisense non-coding RNA in the INK4 locus (ANRIL) and metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) in gingival tissues and blood samples of patients with periodontitis and healthy subjects. Expression of ANRIL was significantly lower in peripheral blood of patients compared with controls (Posterior Beta RE = -1.734, P value = 0.035). However, when diving study participants based on their gender, no significant difference was found between patients and sex-matched controls. Expression of this lncRNA was not different between periodontitis tissues and normal tissues. Expression of MALAT1 was not different between samples obtained from cases and controls. Tissue or blood expressions of ANRIL or MALAT1 were not correlated with age of either patients or controls. There were significant correlations between expression levels of ANRIL and MALAT1 in gingival tissues both in cases (r = 0.62, P < 0.0001) and in controls (r = 0.37, P < 0.0001). However, blood levels of these lncRNAs were not correlated with each other either in cases or in controls. Most notably, there was no significant correlation between expression levels of these lncRNAs in gingival tissues and in the blood of study participants. The current study indicates dysregulation of ANRIL in the peripheral blood of patients with periodontitis in spite of its normal levels in gingival tissues which might reflect disturbance in systemic immune responses in these patients.

Association Analysis Between the rs1899663 Polymorphism of HOTAIR and Risk of Psychiatric Conditions in an Iranian Population.

Recent studies have shown contribution of long non-coding RNAs (lncRNAs) in the pathogenesis of a number of psychiatric disorders. In the current study, we investigated the association between a single nucleotide polymorphism in the lncRNA HOX transcript antisense intergenic RNA (HOTAIR) and risk of diverse neuropsychiatric conditions in Iranian population. The selected polymorphism (rs1899663) is an intronic variant of this lncRNA which has been associated with several cancers in different populations. This SNP was genotyped in 323 individuals with methamphetamine addiction, 55 children with attention-deficit hyperactive disorder (ADHD), 138 patients with bipolar disorder 1 (BPD1), 86 patients with BPD2, 53 patients with major depressive disorder (MDD), and 194 patients with schizophrenia (SCZ). There was no significant association between rs1899663 genotypes and risk of methamphetamine addiction or SCZ in any assessed inheritance model. There was a significant association between rs1899663 SNP and risk of BPD1 in allelic, co-dominant, and dominant models (P values of 0.003, 0.009, and 0.003, respectively). The T allele of this SNP conferred risk of BPD1 (OR (95% CI) = 1.70 (1.20-2.41)). This SNP was associated with risk of BPD2 in allelic and dominant models (P values of 0.02 and 0.04). The T allele of this SNP was revealed to be the risk allele for BPD2 as well (OR (95% CI) = 1.61 (1.09-2.40)). Besides, the mentioned SNP was associated with susceptibility to MDD in allelic and dominant models (P values of 0.01 and 0.03). Finally, the rs1899663 was associated with risk of ADHD in allelic, co-dominant, and dominant models (P values of 3.6E-4, 0.002, and 1.2E-4, respectively). The current investigation highlights the role of rs1899663 in conferring risk of BPD1, BPD2, MDD, and ADHD and suggests a similar underlying genetic background for these conditions.

Upregulation of VEGF-A and correlation between VEGF-A and FLT-1 expressions in Iranian multiple sclerosis patients.

Multiple sclerosis (MS) is among the most common diseases affecting brain and spinal cord. MS progression is characterized by breakdown of blood brain barrier which leads to increased vascular permeability and angiogenesis. Consequently, vascular endothelial growth factor A (VEGF) and its receptors are considered to be important components of MS progression. VEGFA and fms-related tyrosine kinase 1 (FLT1) play important roles in various aspects of MS. In this study, we investigated the relationship between these genes and MS. For this purpose, the expression levels of VEGFA and FLT1 were measured in the blood of 50 relapsing-remitting MS (RR-MS) patients and 50 healthy individuals using TaqMan quantitative real-time PCR. A significant upregulation of VEGFA expression was observed among MS patients compared with controls (p = 0.04). However, the difference in FLT1 gene expression between study groups was insignificant (p = 0.947). In addition, there was a significant positive correlation between VEGFA and FLT1 genes expressions (r = 0.769, p < 0.0001). In spite of the highly complex molecular mechanisms behind this, the findings imply participation of VEGFA in the pathogenesis of MS.

Hepatocellular carcinoma up-regulated long non-coding RNA: a putative marker in multiple sclerosis.

Highly up-regulated in liver cancer (HULC) is a cancer-associated long non-coding RNA (lncRNA) which may regulate expression of other genes by working as a competing RNA for microRNAs. In the current study, we assessed transcript levels of this lncRNA in peripheral blood of multiple sclerosis (MS) patients and healthy persons to evaluate its possible role in the pathogenesis of this inflammatory disease and its diagnostic power. The results of Multilevel Bayesian showed no significant difference between cases and controls (P = 0.002, 95% confidence interval (CI) = [3.08, 13.3]). However, based on the results of Quantile regression, there was a significant difference in HULC expression between cases and controls after controlling the effects of sex and age (P = 0.002, 95% CI = [3.08, 13.3]) which shows different trends in males and females. HULC expression was inversely correlated with age of male subjects but not female subjects. HULC transcript levels had 91.1% accuracy in diagnosis of MS disease (Specificity: 80%, Sensitivity: 86.6%). The diagnostic power of HULC was higher in male subjects aged less than 50 years (AUC = 0.923, Specificity: 80%, Sensitivity: 100%). The present study shows the possibility of application of transcript levels of HULC as diagnostic marker in MS disease. However, future studies with larger sample sizes are necessary to validate our results.

Expression analysis of long non-coding RNAs and their target genes in multiple sclerosis patients.

Multiple sclerosis (MS) is a progressive chronic autoimmune-mediated disease. Recently, long non-coding RNAs (lncRNAs) are characterized to participate in the adjustment of immune responses. Here, we evaluated the expression levels of GSTT1-AS1 and IFNG-AS1 lncRNAs and their targets (TNF and IFNG, respectively) in Iranian MS patients.In this case-control study, 50 relapsing-remitting MS patients and 50 healthy subjects were recruited. Expressions of GSTT1-AS1 and IFNG-AS1 lncRNAs, as well as TNF and IFNG genes, were assessed in their peripheral blood samples by SYBR Green-based Real-time quantitative PCR.Expression levels of GSTT1-AS1 and IFNG-AS1 lncRNAs were both significantly downregulated (p values 0.032 and 0.013, respectively). On the other hand, the expression of TNF and IFNG showed increased levels, however, did not reach statistical significance after our analysis (p > 0.05). Spearman correlation analysis showed that GSTT1-AS1 had a significant positive moderate correlation with IFNG-AS1 (r = 0.541, p < 0.0001), IFNG (r = 0.329, p = 0.001), and TNF (r = 0.204, p = 0.041). Also, IFNG-AS1 revealed the same correlation with IFNG (r = 0.475, p < 0.0001) as well as TNF (r = 0.399, p < 0.0001). Furthermore, GSTT1-AS1 (r = 0.313, p = 0.027) and (IFNG r = 0.478, p < 0.0001) demonstrated a significant positive correlation with age at onset.Briefly, the current study provided for the first time dysregulation of GSTT1-AS1 and IFNG-AS lncRNAs network in MS, which highlights the significant role of epigenetic pathways in this autoimmune disorder. Larger sample size and further investigation assays could shed light on the underlying mechanisms in this area of science.

The Growth Arrest-Specific Transcript 5 (GAS5) and Nuclear Receptor Subfamily 3 Group C Member 1 (NR3C1): Novel Markers Involved in Multiple Sclerosis.

Recent studies have revealed that long noncoding RNAs (lncRNAs) are connected with pathogenesis of neurodegenerative diseases. Additionally, glucocorticoids have fundamental regulatory roles on the immune system, and act as potent therapeutic compounds for autoimmune and inflammatory diseases. The long noncoding RNA growth arrest-specific 5 (GAS5) which accumulates inside the cells in response to cellular starvation/growth arrest, acts as a potent repressor of the glucocorticoid receptor (GR) through its glucocorticoid response element (GRE). The aim of the present study was to investigate the role of lncRNA GAS5 and its downstream target Nuclear Receptor Subfamily 3 Group C Member 1(NR3C1) in the pathogenesis of multiple sclerosis (MS), and to define the role of GAS5 in the regulation of NR3C1 expression. Quantitative polymerase chain reaction was performed for investigating the expression of GAS5 and NR3C1 in MS patients and healthy subjects. We found that GAS5 levels were up-regulated in the MS patients, blood compared with healthy subjects in correlation with NR3C1 expression. Our findings suggest that GAS5 may play on important role in the molecular etiology and treatment of MS.

Dysregulation of long non-coding RNA profile in peripheral blood of multiple sclerosis patients.

Multiple sclerosis (MS) is a chronic autoimmune disorder in which dysregulation or aberrant expressions of several immune-related genes have been noted. More recently, the participation of long non-coding RNAs (lncRNAs) in regulation of immune responses has been highlighted. In the present study, we evaluated expression levels of three lncRNAs named Nuclear Paraspeckle Assembly Transcript 1 (NEAT1), P21 associated ncRNA DNA damage activated (PANDA) and Taurine-up-regulated gene 1 (TUG1) in peripheral blood of 50 relapsing-remitting MS patients and 50 matched healthy subjects. All three lncRNAs have been significantly over-expressed in MS patients compared with healthy subjects. In addition, significant correlations were found between expression levels of these three lncRNAs in the patients group. NEAT1 expression was inversely correlated with age at onset and disease duration in female patients. Moreover, TUG1 expression was inversely correlated with disease duration in female patients. The present study provides further evidences for the role of lncRNAs in pathogenesis of MS.

Expression of TNF- and HNRNPL-related Immunoregulatory Long Non-coding RNA (THRIL) in Acute Myeloid Leukemia: Is There Any Correlation?

Recently, Long noncoding RNAs (lncRNAs) have been described as regulatory factors for several biological mechanisms through regulating the gene expression. Among them the TNF and HNRNPL related immunoregulatory (THRIL) lncRNA may be involved in the pathogenesis of immune-related and inflammatory disease through controlling the expression of the tumor necrosis factor-alpha (TNF-α) expression. In this case-control study, we investigate the THRIL expression in blood 25 samples of de novo acute myeloid leukemia (AML) cases (10 females and 15 males, mean age±SD: 35.1±3.2 years) in comparison to 50 healthy age and sex matched controls (21 females and 29 males, mean age±SD: 34.9± 3.1) using real-time quantitative reverse transcription-PCR (qRT-PCR) in order to explore any association between THRIL and AML. Our results revealed that there was no significant difference in the expression level of THRIL lncRNA between AML patients and healthy individuals (p=0.2, 95% CI=-0.129-28.35). In addition, there was no significant association between male subgroup and THRIL expression as well as females (p=0.08, 95% CI=-0.197-19.251, p=0.4, 95% CI=-0.185-12.041, respectively). In comparison between control group and FAB classification subtypes of AML patients, there was not any significant association. In conclusion, our study showed that THRIL cannot be used as an informative biomarker for AML diagnosis, however, our results need to be clarify by evolution of more cases.

Fas-Antisense Long Noncoding RNA and Acute Myeloid Leukemia: Is There any Relation?

In recent years, lncRNAs have been considered as potential predictive biomarkers for prognosis of different human cancers. One example is the FAS antisense RNA 1 (FAS-AS1) located in the 10q23.31 region which is transcribed from the opposite strand of the FAS gene. FAS has an important role in regulation of apoptotic pathways and there is an inverse correlation between FAS-AS1 expression level and production of the soluble form of Fas, so that it might have potential as a therapeutic target to improve chemotherapy effectiveness. In the present study we therefore evaluated FAS-AS1 expression in blood samples of de novo AML patients and healthy controls using real-time quantitative reverse transcription-PCR (qRT-PCR). Our results indicated that the expression level of FAS-AS1 lncRNA demonstrated no significant difference between AML patients and healthy individuals. We conclude from the obtained data that FAS-AS1 is not an informative and reliable biomarker for AML diagnosis, although our results need to be confirmed in further studies.

STAT5a and STAT6 gene expression levels in multiple sclerosis patients.

Multiple sclerosis (MS) is a complex inflammatory, autoimmune disease of the central nervous system (CNS). The disease pathogenesis is not well defined yet. Cytokines have an important role in inflammation as characteristic feature of the disease. Janus kinase/signal transducers and activators of transcriptions (JAK/STAT) family promote cytokine-mediated cell activation. Failure in the JAK/STAT signaling pathway is associated with the pathological outcome in MS. In this study, we compared the expression levels of STAT5a and STAT6 genes in the blood of 50 relapsing-remitting MS (RR-MS) patients and 50 healthy controls by Taqman Quantitative Real-Time PCR in patients and healthy control group. We found that STAT5a expression was significantly down-regulated (p = .049), whereas STAT6 gene expression was significantly up-regulated (p = .046) in MS patients compared with controls. Moreover, there was significant correlation between the STAT6 gene expression and Kurtzke Expanded Disability Status Scale (EDSS) criterion. However, no significant correlation was demonstrated between the expression of STAT5a gene and clinical findings. Furthermore, there was not significant correlation between expression levels of STAT5a and STAT6 genes. Our findings suggest that STAT5a and STAT6 dysregulation may have a critical role in modification of immune responses leading to imbalance between Th2- and Th1-related cytokines. However, the mechanisms underlying it still remain to be elucidated. Future studies are needed to explore the role of STAT5a and STAT6 as prognostic biomarkers in research, design of experimental therapies or clinical settings of the MS.

Down-regulation of TYK2, CBLB and LMP7 genes expression in relapsing-remitting multiple sclerosis patients treated with interferon-beta.

This study aimed to examine the expression of TYK2, CBLB and LMP7 genes at both mRNA and protein levels in relapsing-remitting MS (RRMS) patients in compare with healthy controls. Seventy-eight RRMS patients treated with IFNß-1a and 79 age- and ethnic-matched healthy subjects were studied. The mRNA expression levels of TYK2, CBLB and LMP7 in PBMCs were quantified by real-time PCR and plasma concentrations of three molecules were measured by ELISA. Results were compared between patients and controls, IFNß-responders and non-responders. Forty-nine of 78 patients were classified as IFNß-responders and 29 cases were non-responders. Significantly down-regulated expression of TYK2, CBLB and LMP7 genes was found in the patients group versus controls (P<0.001). Decreased plasma levels of three molecules were observed in patients compared to controls (P<0.001). IFNß-responders had significantly higher expressions for CBLB (P=0.001) and LMP7 (P=0.02) than non-responders. Also, we observed increased expressions of LMP7 (P=0.39) and CBLB (P=0.02) genes in patients under 30y and increased expression of TYK2 in patients >40years (P=0.002). Our results suggest that expression analysis of TYK2, CBLB and LMP7 genes could be useful for evaluation of T cells immunity and clinical response to IFNß-therapy in RRMS patients.

Ecotropic Viral Integration Site 5 (EVI5) variants are associated with multiple sclerosis in Iranian population.

BACKGROUND: Multiple sclerosis (MS) is a multifactorial disorder with immunological basis. Numerous genetic and environmental factors contribute in its pathogenesis. Several genetic loci have been shown to be associated with MS risk. Among genes whose participation in MS has been evaluated is Ecotropic Viral Integration Site 5 (EVI5). EVI5 is a common site of retroviral integration with a possible role in T-cell lymphomagenesis. METHODS: In the current study, we aimed to confirm association of the single nucleotide polymorphisms (SNPs) within EVI5 gene with MS in 410 relapsing-remitting MS patients and 410 controls from Iranian population. The rs6680578, rs10537781 and rs11810217 genotypes were defined by amplification-refractory mutation system (ARMS)-PCR method. RESULTS: The allele and genotype frequencies of rs6680578 and rs11810217 were not significantly different between cases and controls. However, in the rs10735781 the GG genotype was significantly associated with MS risk in recessive (P = 0.03, OR (95%CI) = 1.84 (1.05-3.19)) and co-dominant models (P = 0.02, OR 95%CI) = 1.90 (1.08-3.35)). In addition, T G T haplotype (rs6680578, rs10735781 and rs11810217 respectively) was associated with MS risk while T C C, A G T and A C T had a protective effect against MS. CONCLUSION: The results of the current study provide further evidences for participation of EVI5 in MS pathogenesis.