Differential expression of STAT3 gene and its regulatory long non-coding RNAs, namely lnc-DC and THRIL, in two eastern Iranian ethnicities with multiple sclerosis.

OBJECTIVE: Genome-wide association studies (GWASs) revealed that variants of STAT3 are associated with multiple sclerosis (MS) risk. There are several studies showing the effect of ethnicity and genetic background on the characteristics of MS. Here, we aimed to investigate STAT3 gene expression status along with its two regulatory long non-coding RNAs, lnc-DC and THRIL, in order to compare the expression of these target genes among two different ethnicities in the east of Iran. METHODS: A case-control study was performed between two groups of MS populations in east of Iran. We recruited individuals with Kurdish ethnicity from North Khorasan and Sistani ethnicity from southeast of Iran. The peripheral blood mononuclear cells were obtained from all participants, and total RNA was extracted. The gene expression of the selected genes was evaluated by qPCR. RESULTS: The expression of THRIL in North Khorasan MS patients was significantly higher than controls (P = 0.03). The results of simultaneous analysis of expression of the target genes (STAT3, THRIL, and lnc-DC) in both ethnic groups failed to show any significant difference between the MS patients and controls (P > 0.05). In addition, the expression of STAT3 and THRIL genes in Sistani MS patients was statistically meaningful lower than healthy controls (P < 0.05). CONCLUSION: To our knowledge, this is the first study that compared the expression of the STAT3 gene and its regulatory molecules between two ethnic groups of Iranian MS patients. We suggested that STAT3 and its associated molecules might be differentially expressed and regulated in MS patients with different genetic background.

Spectrum of alpha-globin gene mutations among premarital Baluch couples in southeastern Iran.

BACKGROUND: Alpha thalassemia (α-thal) is one of the most common hemoglobinopathies worldwide. The aim of this study was to investigate the spectrum of α-thal mutations among premarital Baluch couples in southeastern Iran. SUBJECTS AND METHODS: We assessed 1215 individuals by multiplex gap polymerase chain reaction (gap-PCR) and amplification refractory mutation system (ARMS-PCR). RESULTS: Of the 1215 participants with mean age of 23±5.7 years, 62.3% lived in urban areas, and the rate of consanguineous marriage was 68.1%. Five mutations were identified, the most frequent one was -α (3.7) (rightward) with a frequency of 76.5%, followed by α (-5 nt) (16.8%), α2/ Codon 19(-G) (4%), -α (4.2) (leftward)(2.4%), - -MED (0.3%) among mutated alleles of the α -globin gene. Conclusion : Knowing the alpha-genotype is helpful for genetic counseling, microcytic anemia discrimination and hemoglobinopathy prevention.

Association study of four polymorphisms in the interleukin-7 receptor alpha gene with multiple sclerosis in Eastern Iran.

OBJECTIVES: Multiple sclerosis (MS) is an autoimmune demyelinating disease of the central nervous system (CNS) with unknown etiology. Various genetics and environmental factors contribute to the pathogenesis of the disease. The interleukin-7 receptor alpha chain (IL-7Ra) was identified as the first non-major histocompatibility complex (non-MHC) MS susceptibility locus. In this study we are trying to find the association of IL-7Ra gene polymorphisms with MS susceptibility in Eastern Iran. MATERIALS AND METHODS: A case-control study was performed in two provinces Sistan & Baluchistan and Khorasan with 219 patients and 258 unrelated matched healthy controls, using PCR-RFLP method for four single nucleotide polymorphisms (SNPs) rs7718919, rs11567685, rs11567686 and rs6897932 of IL-7Ra gene. RESULTS: We found a tendency toward association with genotyping analyses in SNP rs7718919 (P=0.048, OR=4.344, and 95% CI=0.892-21.146); also genotype and allele frequency in gender and MS subtype stratification were shown to have significant association with MS. Analysis of two provinces separately showed a significant difference in results of the allele and genotype frequencies. Moreover, haplotyping analysis showed that (GTGC) has an association only in the male secondary-progressive multiple sclerosis (SPMS) patients in comparison to the healthy controls (P=0.043, OR=0.413, and 95% CI=0.179-0.955). CONCLUSION: IL7-Ra could be a susceptible gene to MS within the Eastern Iran population especially after MS and gender stratification.

Expression of suppressor of cytokine signaling 1 (SOCS1) gene dramatically increases in relapsing-remitting multiple sclerosis.

Suppressor of cytokine signaling 1 (SOCS1) is a key regulator of cytokines signaling and plays the most important role in the regulation of the autoimmune responses. The absence of SOCS1 leads to aberrant thymocyte development and systemic inflammation. This study was conducted to evaluate the expression level of SOCS1 mRNA in peripheral blood mononuclear cells (PBMCs) of relapsing-remitting (RR)-multiple sclerosis (MS) patients. In addition, the association of rs243324 SNP with MS and the assessment of this SNP role on the expression level of SOCS1 were aimed to be evaluated. Our results revealed that, SOCS1 mRNA overexpressed (24.5 times) in MS patients versus healthy controls. The rs243324 SNP showed no association with MS susceptibility and this SNP was not in Hardy-Weinberg equilibrium in MS patients. Moreover, there was a significant correlation between SOCS1 expression levels with age of female control group (r=-0.43, P=0.03). Thus, we have probably shown some new evidences for the complex role of SOCS1 gene in the pathogenesis of MS.

The analysis of correlation between IL-1B gene expression and genotyping in multiple sclerosis patients.

IL-1B is released by monocytes, astrocytes and brain endothelial cells and seems to be involved in inflammatory reactions of the central nervous system (CNS) in multiple sclerosis (MS). This study aims to evaluate the expression level of IL-1B mRNA in peripheral blood mononuclear cells (PBMCs), genotype the rs16944 SNP and find out the role of this SNP on the expression level of IL-1B in MS patients. We found that the expression level of IL-1B in MS patients increased 3.336 times more than controls in PBMCs but the rs16944 SNP in the promoter region of IL-1B did not affect the expression level of this gene and there was not association of this SNP with MS in the examined population. Also, our data did not reveal any correlation between normalized expressions of IL-1B gene with age of participants, age of onset, and disease duration.