Multiple sclerosis (MS) is a common disease of the central nervous system.This disease may be ini... more Multiple sclerosis (MS) is a common disease of the central nervous system.This disease may be initiated by either vitamin deficiency or triggered by abnormality in CYP24A1 and vitamin D receptor. In this case-control study, the expression of genes encoding vitamin D receptor (VDR) and CYP24A1 in relapsing-remitting MS (RR-MS) patients was compared with normal individuals in the Iranian population. RNA from whole blood of 50 RR-MS patients (HLA-DRB1*15-negative and responders to interferonbeta with a normal vitamin D level) and 50 normal controls was extracted. The levels of CYP24A1 and VDR expression were measured using real-time quantitative polymerase chain reaction. The RR-MS group had a significantly more than 2 times higher expression level of VDR than the normal group (P=0.04). On the other hand, there was a 0.89 times decrease in the expression level of CYP24A1 in RR-MS patients which was not statistically significant. There was no linear correlation between the risk of expan...
Vitamin D deficiency has been detected in epileptic patients. Vitamin D participates in neuroprot... more Vitamin D deficiency has been detected in epileptic patients. Vitamin D participates in neuroprotection, brain cell proliferation, and differentiation. Consequently, vitamin D supplementation has been suggested as an alternative treatment in epileptic patients. We aimed at assessment of vitamin D signaling pathway in epileptic patients. In the present study, we evaluated vitamin D serum concentration as well as expression of vitamin D receptor (VDR) gene and genes encoding for vitamin D activating enzyme 1-alpha-hydroxylase (CYP27B1) and deactivating enzyme 24-hyroxylase (CYP24A1) in epileptic patients compared with healthy individuals. We found significant lower levels of vitamin D in epileptic patients compared with healthy subjects. Expression analyses showed significant downregulation of VDR expression in peripheral blood of epileptic patients compared with healthy subjects (relative expression (REx) = 0.16, P < 0.001). However, there was no significant difference in CYP24A1 ...
Multiple sclerosis (MS) is a chronic immune-mediated disorder of the central nervous system (CNS)... more 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 co...
Multiple sclerosis (MS) is a complex immune-related disorder of the central nervous system (CNS) ... more 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. However, there is no data regarding relative expression of this gene in peripheral blood of MS patients compared with healthy controls. 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. 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 corr...
This study aimed to examine the expression of TYK2, CBLB and LMP7 genes at both mRNA and protein ... more 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 IFNβ-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, IFNβ-responders and non-responders. Forty-nine of 78 patients were classified as IFNβ-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). IFNβ-responders had significantly higher expressions for CBLB (P=0.001) and LMP7 (P=0.02) than non-responders. Also, we observ...
Iranian journal of allergy, asthma, and immunology, 2017
The association of single nucleotide polymorphisms (SNPs) of the IL-7Rα gene with multiple sclero... more The association of single nucleotide polymorphisms (SNPs) of the IL-7Rα gene with multiple sclerosis (MS) have been documented in various populations. This study aimed to evaluate the genotype distributions of two SNPs, rs6897932 and rs201084372, and the functional association of rs6897932 in relation to IL-7Rα gene expression in a group of Iranian relapsing-remitting MS (RRMS) patients. Genotyping for both SNPs in the IL7Rα gene and relative quantification of mRNA expression for both isoforms of IL-7Rα were performed in 100 RRMS patients and 100 ethnic-matched healthy controls. Higher significant frequencies of the T allele and TT genotype for rs6897932 (C/T) were observed in patients comparing to controls (p=0.006). Higher frequencies of the T allele and the TT and TG genotypes and lower frequencies of the G allele and GG genotypes for rs201084372 (G/A) were found in patients comparing to controls (p<0.0001). A decreased level of mRNA expression for the membrane-bound IL-7Rα ...
The genetic variants of the long non-coding RNA ANRIL (an antisense noncoding RNA in the INK4 loc... more The genetic variants of the long non-coding RNA ANRIL (an antisense noncoding RNA in the INK4 locus) as well as its expression have been shown to be associated with several human diseases including cancers. The aim of this study was to examine the association of ANRIL variants with breast cancer susceptibility in Iranian patients. In this case-control study, we genotyped rs1333045, rs4977574, rs1333048 and rs10757278 single nucleotide polymorphisms (SNPs) in 122 breast can- cer patients as well as in 200 normal age-matched subjects by tetra-primer amplification refractory mutation system polymerase chain reaction (T-ARMS-PCR). The TT genotype at rs1333045 was significantly over-represented among pa- tients (P=0.038) but did not remain significant after multiple-testing correction. In addi- tion, among all observed haplotypes (with SNP order of rs1333045, rs1333048 rs4977574 and rs10757278), four haplotypes were shown to be associated with breast cancer risk. However, after multiple ...
Interleukin 7 receptor alpha (IL7RA) gene that encodes a subunit of IL7 receptor has been reporte... more Interleukin 7 receptor alpha (IL7RA) gene that encodes a subunit of IL7 receptor has been reported to be associated with different immunologic disease. Multiple Sclerosis (MS) patients have shown an aberrant blood level of soluble form of IL7R protein. The genomic changes in the sequence of this gene have been suggested to be correlated with its altered splicing specially, variants in the exon 6 of the gene have been reported to influence the maintenance or skipping of this exon and control the soluble or insoluble form of the final product. In order to evaluate this changes in the IL7RA gene and to determine a possible correlation between these changes and the MS susceptibility the whole sequence of the exon 6 and 7 and their flanking sequences were analyzed. In this regard, we investigate the sequence changes of the exon 6 and 7 of the IL7RA gene in 75 relapsing-remitting MS patients and compare the results with 75 healthy control using sequence analyzing. The results of the seque...
Prostate cancer and benign prostate hyperplasia (BPH) are heterogeneous disorders with high preva... more Prostate cancer and benign prostate hyperplasia (BPH) are heterogeneous disorders with high prevalence among men. The antisense noncoding RNA in the INK4 locus codes for a long noncoding RNA whose participation in cancer has been elucidated. We analyzed rs1333045, rs4977574, rs1333048 and rs10757278 genotypes from this locus in 125 prostate cancer patients, 125 BPH patients as well as 220 normal age-matched subjects by means of tetra-primer amplification refractory mutation system PCR method. The rs1333045 showed no significant difference in allele or genotype frequencies between three groups. However, the other three single nucleotide polymorphisms have been shown to be associated with BPH and prostate cancer risk. Antisense noncoding RNA in the INK4 locus possibly participates in the pathogenesis of these disorders.
Schizophrenia (SCZ) is the most severe chronic mental disorder characterized by abnormal social b... more Schizophrenia (SCZ) is the most severe chronic mental disorder characterized by abnormal social behavior and disrupted emotions and thought. Like other complex neuropsychological disease, SCZ is caused by a combination of genetic and environmental factors but with a high concordance rate. So far, different genetic factors are revealed to be associated with increased risk of developing SCZ. One of the best ways to investigate the genetic basis of the complex disease is to discover the genetic underlying mechanisms of the defective clinical aspects of the patients. In this regard, genes involved in the developmental mechanisms of the brain such as long-term potentiation (LTP) process that is the basis of synaptic plasticity, memory and learning are considered as strong candidates for SCZ. The aim of the present study was to evaluate the expression levels of two genes that are involved in the LTP regulation in the developing and adult brain, Matrix metallopeptidase9 (MMP9) and TIMP met...
Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology, Jan 6, 2017
Multiple sclerosis (MS) is a heterogeneous immune-related demyelinating disorder of central nervo... more Multiple sclerosis (MS) is a heterogeneous immune-related demyelinating disorder of central nervous system with several genetic and environmental factors contributing in its pathogenesis or patients' response to therapies. Myxovirus resistance protein A (MxA) is among the genes which are induced by IFNβ and are involved in the MS pathogenesis and/or response to IFNβ. In the present case-control study, we evaluated the association between three SNPs at nt -123 (A or C, rs17000900), nt -88 (G or T, rs2071430), and nt +20 (A or C, rs464138) and MS risk as well as treatment response in a population of Iranian MS patients including 146 IFNβ responders and 85 non-responders as well as 180 healthy controls. The AGA (-123, -88, +20) haplotype was more frequent in controls compared with MS cases (P = 0.038, OR (95% CI) = 1.77 (1.03-3.02)). Of particular note, the frequency of rs464138 AA genotype was significantly higher in responders compared with non-responders. However, the allele and...
Iranian journal of allergy, asthma, and immunology, 2017
Multiple sclerosis (MS) is an inflammatory, multifocal, immune-mediated disease of the central ne... more Multiple sclerosis (MS) is an inflammatory, multifocal, immune-mediated disease of the central nervous system that women are at a higher risk to acquire than men. Myxovirus resistance protein A (MxA) is used as a predictive marker of bioactivity of interferon-beta (IFN-β) therapy in MS patients. This study was undertaken in west of Iran to investigate gender differences in the expression level of MxA in relapsing-remitting MS (RRMS) patients receiving IFN-β therapy, compared with untreated normal individuals. The expression level of the MxA gene in RRMS samples were compared to untreated normal individuals using the extracted RNA from whole blood of 50 RRMS patients (31 females and 19 males) and 50 normal controls (29 females and 21 males). All patients were HLA-DRB1*15 negative and responded to IFN-β with a normal vitamin D level. The level of MxA gene expression was measured by quantitative RT-PCR. The levels of gene expression were decreased in RRMS patients compared with normal ...
Journal of molecular neuroscience : MN, Jan 11, 2017
Vascular endothelial growth factor (VEGF) and its receptor kinase insert domain-containing recept... more Vascular endothelial growth factor (VEGF) and its receptor kinase insert domain-containing receptor (KDR) pathway trigger the process of angiogenesis as well as inflammation, which contributes to the development and progression of demyelinating lesions in multiple sclerosis. This work is a case-control study comprising of a total of 400 subjects with multiple sclerosis and 400 healthy controls. Participants were subjected to neurological examination and peripheral blood sampling for genotyping. Polymorphisms in the VEGF and KDR genes were assessed using the restriction fragment length polymorphism (RFLP-PCR) method. A significantly higher frequency of the T allele and TT genotype of the VEGF 936C > T (rs3025039) polymorphism was found in the multiple sclerosis group than in the healthy control group (P = 0.01 [OR = 1.41] and P = 0.01 [OR = 3.12], respectively). In addition, VEGF 936C > T showed an association with patients in a recessive model. However, the KDR -604T > C ...
Multiple sclerosis (MS) is a heterogeneous chronic immune-mediated disorder of the central nervou... more Multiple sclerosis (MS) is a heterogeneous chronic immune-mediated disorder of the central nervous system (CNS) with several environmental and genetic factors participating in its development and disease course. Interferon (IFN)-β therapy is considered as the first line treatment in this disorder. The present study enrolled 231 relapsing-remitting MS patients who were diagnosed as IFN-β responders (n = 146) and non-responders (n = 85). Serum cytokine levels were analyzed by commercially available ELISA kits in distinct groups based on HLA-A,-B and-DRB1 alleles. IFN-γ levels were significantly higher in responders compared with non-responders, whereas IL-17A and IL-6 had the opposite trend. The levels of IL-10 and IL-4 were not significantly different between two groups. IFN-γ and IL-17A levels were associated with response to IFN-β. Comparison of cytokine levels revealed higher IFN-γ levels in HLA-DRB1 * 04 positive patients (n = 72) compared with HLA-DRB1 * 04 negative patients (n = 159). In responder group, patients who were positive for HLA-DRB1 * 15 had significantly higher levels of IL-6 compared to HLA-DRB1 * 15 negative patients. IL-17A levels tend to be higher in responder patients who were positive for HLA-DRB1 * 04 compared with those were negative for the same allele. This study suggests that the serum levels of pro-and anti-inflammatory cytokines are different among IFN-β responders and non-responders. Future studies are needed to confirm their efficiency in determination of response to IFN-β in MS patients.
One of the recent aspects in the cancer research is about the investigation of the etiological ro... more One of the recent aspects in the cancer research is about the investigation of the etiological role of long noncoding RNAs as a new regulator for the expression of proto-oncogenes or tumor suppressor genes in cancer. Among them HOX transcript antisense RNA (HOTAIR) is increasingly indicated to be deregulated in different cancers such as AML. According to the important regulatory role the gene in the developing and prognosis of the hematological malignancies we investigate whether there is an association between rs12826786, rs1899663, and rs4759314 common polymorphisms of the gene with AML patients. The results have shown no relation between any of the analyzed Single Nucleotide Polymorphisms and AML either in genotypic frequencies or in haplotype analysis. The data derived from the present study suggested that pathogenic role of the HOTAIR to increase the susceptibility of AML should be considered from other aspects and further analysis are needed to explore the exact mechanism underlying the pathogenesis.
Prostate cancer and benign prostate hyperplasia (BPH) are heterogeneous disorders with a wide arr... more Prostate cancer and benign prostate hyperplasia (BPH) are heterogeneous disorders with a wide array of clinical presentations and high prevalence among men. Several protein coding genes as well as non-coding genes have been shown to contribute in prostate cancer and BPH risk. Among non-coding genes whose contribution in tumorigenesis has been identified is HOX transcript antisense RNA (HOTAIR). In the present study we aimed at identification of the associations between three HOTAIR polymorphisms (rs12826786, rs1899663 and rs4759314) and risk of prostate cancer and BPH by the means of tetra-primer ARMS-PCR in a population of 128 Iranian prostate cancer patients, 143 BPH patients and 250 normal male controls. The study showed that rs1899663 T allele was associated with BPH risk. Comparison between prostate cancer and BPH groups showed that rs1899663 is associated with cancer risk in co-dominant, dominant and recessive inheritance models. The rs12826786 T allele was significantly more ...
BACKGROUND: Multiple sclerosis (MS) as an auto-immune disease is an inflammatory, demyelinating d... more BACKGROUND: Multiple sclerosis (MS) as an auto-immune disease is an inflammatory, demyelinating disease of the central nervous system. Certain genes have shown to be involved in the initiation of MS but the specific role of some of them, e.g. IFNAR1 has not been identified in certain populations yet. OBJECTIVE: The IFNAR1 as a type I membrane protein shapes one of the two chains of a receptor for interferons alpha and beta. METHODS: To find out how IFNAR1 functions in the Iranian population, the researchers compared the expression level of this gene in relapsing-remitting MS (RR-MS) samples with normal individuals. RNA from the whole blood of 50 RR-MS patients and 50 normal controls were extracted. All patients were HLA-DRB1*15 negative and were responders to interferon-beta with a normal vitamin D level. The level of IFNAR1 gene expression was measured using quantitative RT-PCR. RESULTS: According to the results the RR-MS patients manifested a statistically higher expression level of IFNAR1 than their normal counterparts (p = 0.012). Age-wise, females between the ages, 30 to 40 had a significant increase (p = 0.046) but males under 30 showed a statistically meaningful decrease in the expression level (p = 0.04). In terms of sex, only the female patients manifested a statistically significant increase in IFNAR1 (p = 0.004). CONCLUSIONS: The overall results show an increase in IFNAR1 level in MS patients treated with IFN-B.
Multiple sclerosis (MS) is a chronic disorder resulting from destruction of the myelin or insulat... more Multiple sclerosis (MS) is a chronic disorder resulting from destruction of the myelin or insulating covers of neurons in the central nervous system (CNS). Several lines of evidence suggest a role for immune response in the occurrence and progression of this disorder. Several disease-modifying agents (DMA) including b-interferons (IFNb) are being used in MS patients in order to stop the disease at the early inflammatory stage, postpone disease progression and diminish future disability. Phospholipase D1 (PLD1) is a critical enzyme responsible for the making lipid second messenger phosphatidic acid. It has an established function in regulation of immune response. In the present study we have evaluated PLD1 transcript levels and plasma concentrations in 78 relapsingremitting MS (RRMS) patients as well as 78 normal ageand sex-matched healthy subjects using real-time quantitative RT-PCR and enzyme-linked immunosorbent assay (ELISA), respectively. Significant PLD1 down-regulation has been observed in total MS patients compared with controls (P \ 0.001) as well as IFN-b responders (P = 0.034) and non-responders (P \ 0.001) compared with controls, respectively. However, a significant up-regulation has been detected in IFN-b responders compared with non-responders (P = 0.047). In both males and females groups, significant down-regulations have been detected in patients compared with controls (P = 0.014 and P = 0.002, respectively). The same results have been detected in PLD1 plasma concentrations. In conclusion, PLD1 transcripts in blood and its plasma concentrations can be used as putative biomarkers for evaluation of therapeutic responses to IFN-b in RRMS patients. However, this result should be validated in future studies.
Ras-like without CAAX2 (RIT2) which encodes a GTP-binding protein has recently been reported as a... more Ras-like without CAAX2 (RIT2) which encodes a GTP-binding protein has recently been reported as a new susceptibility gene for Autism Spectrum Disorders (ASD) in a genome-wide association study. Since the gene is suggested to be involved in the pathogenesis of different neurological diseases, we investigated the association of two single nucleotide polymorphisms (SNP) rs16976358 and rs4130047 of this gene with ASD in Iranian patients. A total of 1004 individuals, comprising 532 ASD cases and 472 healthy subjects participated in this study. Allele frequency analyses showed significant over-presentation of rs16976358-C allele in cases versus controls (P < 0.0001). In addition, rs16976358 CC genotype (OR (95% CI) =3.57(1.72-7.69) and P < 0.0001) and rs4130047 CC genotype (OR (95% CI) =0.64(0.43-0.97) and P = 0.035) were associated with ASD in recessive inheritance model. Besides, haplotype analysis demonstrated an association between the C/T haplotype block (rs16976358/ rs4130047) and ASD (OR (95%CI) = 0.44 (0.31-0.62), P < 0.0001). Altogether, our findings provided additional confirmation for the RIT2 gene participation in ASD risk and suggested the rs16976358 variant as a possible genetic risk factor for this disorder.
Multiple sclerosis (MS) is a chronic autoimmune disease, and the most common cause of nontraumati... more Multiple sclerosis (MS) is a chronic autoimmune disease, and the most common cause of nontraumatic disability in young people. The etiology of this disease is not well defined yet. Cytokines play an important role in differentiation, maturation and survival of a wide range of cells, including cells of the immune system. Suppressor of cytokine signaling (SOCS) proteins are the most important regulators of this cytokine signaling pathway. The aim of present study was to compare the expression levels of SOCS1, SOCS2, SOCS3 and SOCS5 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 observed that SOCS1 and SOCS5 expression was significantly down-regulated (P=0.045 and P=0.044, respectively); whereas, no significant difference was observed between MS patients and controls for SOCS2 and SOCS3 gene expression (P=0.747 and P=0.439, respectively). In addition, there was no significant correlation between the expression of SOCS1, SOCS2, SOCS3 and SOCS5 genes and clinical findings, such as the level of physical disability in the MS patients according to the Kurtzke Expanded Disability Status Scale (EDSS) criterion and disease duration. However, a significant positive correlation was observed between expression levels of SOCS genes. This study shows that loss of balance among various members of the SOCS family proteins may contribute to pathophysiology of multiple sclerosis.
Multiple sclerosis (MS) is a common disease of the central nervous system.This disease may be ini... more Multiple sclerosis (MS) is a common disease of the central nervous system.This disease may be initiated by either vitamin deficiency or triggered by abnormality in CYP24A1 and vitamin D receptor. In this case-control study, the expression of genes encoding vitamin D receptor (VDR) and CYP24A1 in relapsing-remitting MS (RR-MS) patients was compared with normal individuals in the Iranian population. RNA from whole blood of 50 RR-MS patients (HLA-DRB1*15-negative and responders to interferonbeta with a normal vitamin D level) and 50 normal controls was extracted. The levels of CYP24A1 and VDR expression were measured using real-time quantitative polymerase chain reaction. The RR-MS group had a significantly more than 2 times higher expression level of VDR than the normal group (P=0.04). On the other hand, there was a 0.89 times decrease in the expression level of CYP24A1 in RR-MS patients which was not statistically significant. There was no linear correlation between the risk of expan...
Vitamin D deficiency has been detected in epileptic patients. Vitamin D participates in neuroprot... more Vitamin D deficiency has been detected in epileptic patients. Vitamin D participates in neuroprotection, brain cell proliferation, and differentiation. Consequently, vitamin D supplementation has been suggested as an alternative treatment in epileptic patients. We aimed at assessment of vitamin D signaling pathway in epileptic patients. In the present study, we evaluated vitamin D serum concentration as well as expression of vitamin D receptor (VDR) gene and genes encoding for vitamin D activating enzyme 1-alpha-hydroxylase (CYP27B1) and deactivating enzyme 24-hyroxylase (CYP24A1) in epileptic patients compared with healthy individuals. We found significant lower levels of vitamin D in epileptic patients compared with healthy subjects. Expression analyses showed significant downregulation of VDR expression in peripheral blood of epileptic patients compared with healthy subjects (relative expression (REx) = 0.16, P < 0.001). However, there was no significant difference in CYP24A1 ...
Multiple sclerosis (MS) is a chronic immune-mediated disorder of the central nervous system (CNS)... more 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 co...
Multiple sclerosis (MS) is a complex immune-related disorder of the central nervous system (CNS) ... more 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. However, there is no data regarding relative expression of this gene in peripheral blood of MS patients compared with healthy controls. 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. 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 corr...
This study aimed to examine the expression of TYK2, CBLB and LMP7 genes at both mRNA and protein ... more 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 IFNβ-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, IFNβ-responders and non-responders. Forty-nine of 78 patients were classified as IFNβ-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). IFNβ-responders had significantly higher expressions for CBLB (P=0.001) and LMP7 (P=0.02) than non-responders. Also, we observ...
Iranian journal of allergy, asthma, and immunology, 2017
The association of single nucleotide polymorphisms (SNPs) of the IL-7Rα gene with multiple sclero... more The association of single nucleotide polymorphisms (SNPs) of the IL-7Rα gene with multiple sclerosis (MS) have been documented in various populations. This study aimed to evaluate the genotype distributions of two SNPs, rs6897932 and rs201084372, and the functional association of rs6897932 in relation to IL-7Rα gene expression in a group of Iranian relapsing-remitting MS (RRMS) patients. Genotyping for both SNPs in the IL7Rα gene and relative quantification of mRNA expression for both isoforms of IL-7Rα were performed in 100 RRMS patients and 100 ethnic-matched healthy controls. Higher significant frequencies of the T allele and TT genotype for rs6897932 (C/T) were observed in patients comparing to controls (p=0.006). Higher frequencies of the T allele and the TT and TG genotypes and lower frequencies of the G allele and GG genotypes for rs201084372 (G/A) were found in patients comparing to controls (p<0.0001). A decreased level of mRNA expression for the membrane-bound IL-7Rα ...
The genetic variants of the long non-coding RNA ANRIL (an antisense noncoding RNA in the INK4 loc... more The genetic variants of the long non-coding RNA ANRIL (an antisense noncoding RNA in the INK4 locus) as well as its expression have been shown to be associated with several human diseases including cancers. The aim of this study was to examine the association of ANRIL variants with breast cancer susceptibility in Iranian patients. In this case-control study, we genotyped rs1333045, rs4977574, rs1333048 and rs10757278 single nucleotide polymorphisms (SNPs) in 122 breast can- cer patients as well as in 200 normal age-matched subjects by tetra-primer amplification refractory mutation system polymerase chain reaction (T-ARMS-PCR). The TT genotype at rs1333045 was significantly over-represented among pa- tients (P=0.038) but did not remain significant after multiple-testing correction. In addi- tion, among all observed haplotypes (with SNP order of rs1333045, rs1333048 rs4977574 and rs10757278), four haplotypes were shown to be associated with breast cancer risk. However, after multiple ...
Interleukin 7 receptor alpha (IL7RA) gene that encodes a subunit of IL7 receptor has been reporte... more Interleukin 7 receptor alpha (IL7RA) gene that encodes a subunit of IL7 receptor has been reported to be associated with different immunologic disease. Multiple Sclerosis (MS) patients have shown an aberrant blood level of soluble form of IL7R protein. The genomic changes in the sequence of this gene have been suggested to be correlated with its altered splicing specially, variants in the exon 6 of the gene have been reported to influence the maintenance or skipping of this exon and control the soluble or insoluble form of the final product. In order to evaluate this changes in the IL7RA gene and to determine a possible correlation between these changes and the MS susceptibility the whole sequence of the exon 6 and 7 and their flanking sequences were analyzed. In this regard, we investigate the sequence changes of the exon 6 and 7 of the IL7RA gene in 75 relapsing-remitting MS patients and compare the results with 75 healthy control using sequence analyzing. The results of the seque...
Prostate cancer and benign prostate hyperplasia (BPH) are heterogeneous disorders with high preva... more Prostate cancer and benign prostate hyperplasia (BPH) are heterogeneous disorders with high prevalence among men. The antisense noncoding RNA in the INK4 locus codes for a long noncoding RNA whose participation in cancer has been elucidated. We analyzed rs1333045, rs4977574, rs1333048 and rs10757278 genotypes from this locus in 125 prostate cancer patients, 125 BPH patients as well as 220 normal age-matched subjects by means of tetra-primer amplification refractory mutation system PCR method. The rs1333045 showed no significant difference in allele or genotype frequencies between three groups. However, the other three single nucleotide polymorphisms have been shown to be associated with BPH and prostate cancer risk. Antisense noncoding RNA in the INK4 locus possibly participates in the pathogenesis of these disorders.
Schizophrenia (SCZ) is the most severe chronic mental disorder characterized by abnormal social b... more Schizophrenia (SCZ) is the most severe chronic mental disorder characterized by abnormal social behavior and disrupted emotions and thought. Like other complex neuropsychological disease, SCZ is caused by a combination of genetic and environmental factors but with a high concordance rate. So far, different genetic factors are revealed to be associated with increased risk of developing SCZ. One of the best ways to investigate the genetic basis of the complex disease is to discover the genetic underlying mechanisms of the defective clinical aspects of the patients. In this regard, genes involved in the developmental mechanisms of the brain such as long-term potentiation (LTP) process that is the basis of synaptic plasticity, memory and learning are considered as strong candidates for SCZ. The aim of the present study was to evaluate the expression levels of two genes that are involved in the LTP regulation in the developing and adult brain, Matrix metallopeptidase9 (MMP9) and TIMP met...
Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology, Jan 6, 2017
Multiple sclerosis (MS) is a heterogeneous immune-related demyelinating disorder of central nervo... more Multiple sclerosis (MS) is a heterogeneous immune-related demyelinating disorder of central nervous system with several genetic and environmental factors contributing in its pathogenesis or patients' response to therapies. Myxovirus resistance protein A (MxA) is among the genes which are induced by IFNβ and are involved in the MS pathogenesis and/or response to IFNβ. In the present case-control study, we evaluated the association between three SNPs at nt -123 (A or C, rs17000900), nt -88 (G or T, rs2071430), and nt +20 (A or C, rs464138) and MS risk as well as treatment response in a population of Iranian MS patients including 146 IFNβ responders and 85 non-responders as well as 180 healthy controls. The AGA (-123, -88, +20) haplotype was more frequent in controls compared with MS cases (P = 0.038, OR (95% CI) = 1.77 (1.03-3.02)). Of particular note, the frequency of rs464138 AA genotype was significantly higher in responders compared with non-responders. However, the allele and...
Iranian journal of allergy, asthma, and immunology, 2017
Multiple sclerosis (MS) is an inflammatory, multifocal, immune-mediated disease of the central ne... more Multiple sclerosis (MS) is an inflammatory, multifocal, immune-mediated disease of the central nervous system that women are at a higher risk to acquire than men. Myxovirus resistance protein A (MxA) is used as a predictive marker of bioactivity of interferon-beta (IFN-β) therapy in MS patients. This study was undertaken in west of Iran to investigate gender differences in the expression level of MxA in relapsing-remitting MS (RRMS) patients receiving IFN-β therapy, compared with untreated normal individuals. The expression level of the MxA gene in RRMS samples were compared to untreated normal individuals using the extracted RNA from whole blood of 50 RRMS patients (31 females and 19 males) and 50 normal controls (29 females and 21 males). All patients were HLA-DRB1*15 negative and responded to IFN-β with a normal vitamin D level. The level of MxA gene expression was measured by quantitative RT-PCR. The levels of gene expression were decreased in RRMS patients compared with normal ...
Journal of molecular neuroscience : MN, Jan 11, 2017
Vascular endothelial growth factor (VEGF) and its receptor kinase insert domain-containing recept... more Vascular endothelial growth factor (VEGF) and its receptor kinase insert domain-containing receptor (KDR) pathway trigger the process of angiogenesis as well as inflammation, which contributes to the development and progression of demyelinating lesions in multiple sclerosis. This work is a case-control study comprising of a total of 400 subjects with multiple sclerosis and 400 healthy controls. Participants were subjected to neurological examination and peripheral blood sampling for genotyping. Polymorphisms in the VEGF and KDR genes were assessed using the restriction fragment length polymorphism (RFLP-PCR) method. A significantly higher frequency of the T allele and TT genotype of the VEGF 936C > T (rs3025039) polymorphism was found in the multiple sclerosis group than in the healthy control group (P = 0.01 [OR = 1.41] and P = 0.01 [OR = 3.12], respectively). In addition, VEGF 936C > T showed an association with patients in a recessive model. However, the KDR -604T > C ...
Multiple sclerosis (MS) is a heterogeneous chronic immune-mediated disorder of the central nervou... more Multiple sclerosis (MS) is a heterogeneous chronic immune-mediated disorder of the central nervous system (CNS) with several environmental and genetic factors participating in its development and disease course. Interferon (IFN)-β therapy is considered as the first line treatment in this disorder. The present study enrolled 231 relapsing-remitting MS patients who were diagnosed as IFN-β responders (n = 146) and non-responders (n = 85). Serum cytokine levels were analyzed by commercially available ELISA kits in distinct groups based on HLA-A,-B and-DRB1 alleles. IFN-γ levels were significantly higher in responders compared with non-responders, whereas IL-17A and IL-6 had the opposite trend. The levels of IL-10 and IL-4 were not significantly different between two groups. IFN-γ and IL-17A levels were associated with response to IFN-β. Comparison of cytokine levels revealed higher IFN-γ levels in HLA-DRB1 * 04 positive patients (n = 72) compared with HLA-DRB1 * 04 negative patients (n = 159). In responder group, patients who were positive for HLA-DRB1 * 15 had significantly higher levels of IL-6 compared to HLA-DRB1 * 15 negative patients. IL-17A levels tend to be higher in responder patients who were positive for HLA-DRB1 * 04 compared with those were negative for the same allele. This study suggests that the serum levels of pro-and anti-inflammatory cytokines are different among IFN-β responders and non-responders. Future studies are needed to confirm their efficiency in determination of response to IFN-β in MS patients.
One of the recent aspects in the cancer research is about the investigation of the etiological ro... more One of the recent aspects in the cancer research is about the investigation of the etiological role of long noncoding RNAs as a new regulator for the expression of proto-oncogenes or tumor suppressor genes in cancer. Among them HOX transcript antisense RNA (HOTAIR) is increasingly indicated to be deregulated in different cancers such as AML. According to the important regulatory role the gene in the developing and prognosis of the hematological malignancies we investigate whether there is an association between rs12826786, rs1899663, and rs4759314 common polymorphisms of the gene with AML patients. The results have shown no relation between any of the analyzed Single Nucleotide Polymorphisms and AML either in genotypic frequencies or in haplotype analysis. The data derived from the present study suggested that pathogenic role of the HOTAIR to increase the susceptibility of AML should be considered from other aspects and further analysis are needed to explore the exact mechanism underlying the pathogenesis.
Prostate cancer and benign prostate hyperplasia (BPH) are heterogeneous disorders with a wide arr... more Prostate cancer and benign prostate hyperplasia (BPH) are heterogeneous disorders with a wide array of clinical presentations and high prevalence among men. Several protein coding genes as well as non-coding genes have been shown to contribute in prostate cancer and BPH risk. Among non-coding genes whose contribution in tumorigenesis has been identified is HOX transcript antisense RNA (HOTAIR). In the present study we aimed at identification of the associations between three HOTAIR polymorphisms (rs12826786, rs1899663 and rs4759314) and risk of prostate cancer and BPH by the means of tetra-primer ARMS-PCR in a population of 128 Iranian prostate cancer patients, 143 BPH patients and 250 normal male controls. The study showed that rs1899663 T allele was associated with BPH risk. Comparison between prostate cancer and BPH groups showed that rs1899663 is associated with cancer risk in co-dominant, dominant and recessive inheritance models. The rs12826786 T allele was significantly more ...
BACKGROUND: Multiple sclerosis (MS) as an auto-immune disease is an inflammatory, demyelinating d... more BACKGROUND: Multiple sclerosis (MS) as an auto-immune disease is an inflammatory, demyelinating disease of the central nervous system. Certain genes have shown to be involved in the initiation of MS but the specific role of some of them, e.g. IFNAR1 has not been identified in certain populations yet. OBJECTIVE: The IFNAR1 as a type I membrane protein shapes one of the two chains of a receptor for interferons alpha and beta. METHODS: To find out how IFNAR1 functions in the Iranian population, the researchers compared the expression level of this gene in relapsing-remitting MS (RR-MS) samples with normal individuals. RNA from the whole blood of 50 RR-MS patients and 50 normal controls were extracted. All patients were HLA-DRB1*15 negative and were responders to interferon-beta with a normal vitamin D level. The level of IFNAR1 gene expression was measured using quantitative RT-PCR. RESULTS: According to the results the RR-MS patients manifested a statistically higher expression level of IFNAR1 than their normal counterparts (p = 0.012). Age-wise, females between the ages, 30 to 40 had a significant increase (p = 0.046) but males under 30 showed a statistically meaningful decrease in the expression level (p = 0.04). In terms of sex, only the female patients manifested a statistically significant increase in IFNAR1 (p = 0.004). CONCLUSIONS: The overall results show an increase in IFNAR1 level in MS patients treated with IFN-B.
Multiple sclerosis (MS) is a chronic disorder resulting from destruction of the myelin or insulat... more Multiple sclerosis (MS) is a chronic disorder resulting from destruction of the myelin or insulating covers of neurons in the central nervous system (CNS). Several lines of evidence suggest a role for immune response in the occurrence and progression of this disorder. Several disease-modifying agents (DMA) including b-interferons (IFNb) are being used in MS patients in order to stop the disease at the early inflammatory stage, postpone disease progression and diminish future disability. Phospholipase D1 (PLD1) is a critical enzyme responsible for the making lipid second messenger phosphatidic acid. It has an established function in regulation of immune response. In the present study we have evaluated PLD1 transcript levels and plasma concentrations in 78 relapsingremitting MS (RRMS) patients as well as 78 normal ageand sex-matched healthy subjects using real-time quantitative RT-PCR and enzyme-linked immunosorbent assay (ELISA), respectively. Significant PLD1 down-regulation has been observed in total MS patients compared with controls (P \ 0.001) as well as IFN-b responders (P = 0.034) and non-responders (P \ 0.001) compared with controls, respectively. However, a significant up-regulation has been detected in IFN-b responders compared with non-responders (P = 0.047). In both males and females groups, significant down-regulations have been detected in patients compared with controls (P = 0.014 and P = 0.002, respectively). The same results have been detected in PLD1 plasma concentrations. In conclusion, PLD1 transcripts in blood and its plasma concentrations can be used as putative biomarkers for evaluation of therapeutic responses to IFN-b in RRMS patients. However, this result should be validated in future studies.
Ras-like without CAAX2 (RIT2) which encodes a GTP-binding protein has recently been reported as a... more Ras-like without CAAX2 (RIT2) which encodes a GTP-binding protein has recently been reported as a new susceptibility gene for Autism Spectrum Disorders (ASD) in a genome-wide association study. Since the gene is suggested to be involved in the pathogenesis of different neurological diseases, we investigated the association of two single nucleotide polymorphisms (SNP) rs16976358 and rs4130047 of this gene with ASD in Iranian patients. A total of 1004 individuals, comprising 532 ASD cases and 472 healthy subjects participated in this study. Allele frequency analyses showed significant over-presentation of rs16976358-C allele in cases versus controls (P < 0.0001). In addition, rs16976358 CC genotype (OR (95% CI) =3.57(1.72-7.69) and P < 0.0001) and rs4130047 CC genotype (OR (95% CI) =0.64(0.43-0.97) and P = 0.035) were associated with ASD in recessive inheritance model. Besides, haplotype analysis demonstrated an association between the C/T haplotype block (rs16976358/ rs4130047) and ASD (OR (95%CI) = 0.44 (0.31-0.62), P < 0.0001). Altogether, our findings provided additional confirmation for the RIT2 gene participation in ASD risk and suggested the rs16976358 variant as a possible genetic risk factor for this disorder.
Multiple sclerosis (MS) is a chronic autoimmune disease, and the most common cause of nontraumati... more Multiple sclerosis (MS) is a chronic autoimmune disease, and the most common cause of nontraumatic disability in young people. The etiology of this disease is not well defined yet. Cytokines play an important role in differentiation, maturation and survival of a wide range of cells, including cells of the immune system. Suppressor of cytokine signaling (SOCS) proteins are the most important regulators of this cytokine signaling pathway. The aim of present study was to compare the expression levels of SOCS1, SOCS2, SOCS3 and SOCS5 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 observed that SOCS1 and SOCS5 expression was significantly down-regulated (P=0.045 and P=0.044, respectively); whereas, no significant difference was observed between MS patients and controls for SOCS2 and SOCS3 gene expression (P=0.747 and P=0.439, respectively). In addition, there was no significant correlation between the expression of SOCS1, SOCS2, SOCS3 and SOCS5 genes and clinical findings, such as the level of physical disability in the MS patients according to the Kurtzke Expanded Disability Status Scale (EDSS) criterion and disease duration. However, a significant positive correlation was observed between expression levels of SOCS genes. This study shows that loss of balance among various members of the SOCS family proteins may contribute to pathophysiology of multiple sclerosis.
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