Analysis of Single Nucleotide Polymorphisms in HLA-DRA, IL2RA, and HMGB1 Genes  in Multiple Sclerosis

Asouri, Mohsen; Rokni, Hamid Alinejad; Sahraian, Mohammad Ali; Fattahi, Sadegh; Motamed, Nima; Doosti, Rozita; Rahimi, Hamzeh; Lotfi, Maryam; Moslemi, Azam; Karimpoor, Morteza; Mahboudi, Fereidoun; Akhavan‐Niaki, Haleh

doi:10.29252/rbmb.9.2.199

Cited by 8 publications

(7 citation statements)

References 20 publications

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“…HLA-DRA is shown to be a susceptibility gene for multiple sclerosis in the Australian population. Polymorphisms of rs4935356, rs3177928, and rs7197 of the HLA-DRA gene have been associated with multiple sclerosis in the Iranian population [ 31 ]. In addition, HLA-DRA gene polymorphisms are associated with the clinical course and long-term prognosis of ulcerative colitis [ 32 ].…”

Section: Discussionmentioning

confidence: 99%

“…Recent studies have shown that SNP at rs3177928 is associated with sarcoidosis [33], as well as lipid metabolism and inflammatory mechanisms [34][35][36][37]. More recently, rs7197 SNP has been found to be closely related to the antibody response to viral elements such as capsid antigen of Epstein-Barr virus, and it is speculated that rs7197 genetic variation may play a role in disease susceptibility through immune-mediated specific microbial genes [31]. Combining our study with previous in vitro and in vivo evidence that Epstein-Barr virus infection is associated with TRAb production and GD occurrence [38,39], it is reasonable to infer that there is a natural association between rs3177928, rs7197 polymorphisms, and AITD development.…”

Section: Discussionmentioning

confidence: 99%

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HLA‐DRA Gene Polymorphisms Are Associated with Graves’ Disease as an Autoimmune Thyroid Disease

Zhu

Yao

Cai

et al. 2022

BioMed Research International

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Background. Autoimmune thyroid disease (AITD), one of the most prevalent organ-specific autoimmune diseases, mainly includes Graves’ disease (GD) and Hashimoto’s thyroiditis (HT). This study was aimed at researching the association between AITD and single nucleotide polymorphisms (SNPs) of the HLA-DRA gene. Methods. Using Hi-SNP high-throughput sequencing technology, we detected the distribution of three SNPs (rs3177928, rs7197, and rs3129878) of HLA-DRA genotypes in 1033 AITD patients (634 GD and 399 HT ones) and 791 healthy volunteers in Chinese Han Population. Chi-square test, multivariate logistic regression, and haplotype analysis were performed by SPSS and Haploview software to analyze the relationship between HLA-DRA gene polymorphisms and AITD. Results. The results show that allele frequency and genotype distribution of rs3177928 and rs7197 were correlated with AITD and GD compared with the healthy control group, but not with HT. Rs3177928 and rs7197 were correlated with AITD and HT in the allele model, dominant model, and overdominant model before and after gender and age adjustment, but not with HT. In addition, we found that two loci (rs3177928 and rs7197) constituted a linkage disequilibrium (LD) region, and haplotype AA was associated with AITD and GD. However, we found no association between rs3129878 and AITD. Conclusion. Our study is the first to find that rs3177928 and rs7197 of HLA-DRA are significantly correlated with AITD and GD in the Chinese Han population. This will help further reveal the pathogenesis of AITD and provide new candidate genes for the prediction or treatment of AITD.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

HLA‐DRA Gene Polymorphisms Are Associated with Graves’ Disease as an Autoimmune Thyroid Disease

Zhu

Yao

Cai

et al. 2022

BioMed Research International

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“…[76], BTK (Bruton tyrosine kinase) [77], C7 [78], PLA2G7 [79], SOCS3 [80], OLR1 [81], LIPA (lipase A, lysosomal acid type) [82], CD86 [83], TLR5 [ [100], AGRN (agrin) [101] and GP6 [102] have been shown as a promising biomarkers in Alzheimer's disease. Field et al [103], Lincoln et al [104], Ziliotto et al [105], El Sharkawi et al [106], Cossins et al [107], Mirowska-Guzel et al [108], Asouri et al [109], Cardamone et al [110], Begovich et al [111], Bennetts et al [112], Iparraguirre et al [113] and Oldoni et al [114] reported that HLA-DPB1, HLA-DQA1, CCL18, CCL20, MMP7, IL1A, IL2RA, CYBB (cytochrome b-245 beta chain), PTPN22, HLA-DMB, ANXA2 and CHIT1expression were associated with progression of multiple sclerosis, but these genes might be liable for advancement of dementia. Chang et al [115], Jamshidi et al [116], Campolo et al [117], Bottero et al [118], Gao et al [119], Haga et al [120], Klaver et al [121], Greenbaum et al [122] and Aguirre et al [123] reported that expression of HLA-DQB1, HLA-DRA, TLR7, TLR8, PTPRC (protein tyrosine phosphatase receptor type C), OSMR (oncostatin M receptor), FABP5, LAMP2, CHRNA5 and IL13RA1 could be an index for Parkinson's disease progression, but these genes might be responsible for progression of dementia.…”

Section: Discussionmentioning

confidence: 99%

Identification of Key Pathways and Genes in Dementia via Integrated Bioinformatics Analysis

Vastrad¹,

Vastrad²

2021

Preprint

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To provide a better understanding of dementia at the molecular level, this study aimed to identify the genes and key pathways associated with dementia by using integrated bioinformatics analysis. Based on the expression profiling by high throughput sequencing dataset GSE153960 derived from the Gene Expression Omnibus (GEO), the differentially expressed genes (DEGs) between patients with dementia and healthy controls were identified. With DEGs, we performed a series of functional enrichment analyses. Then, a protein protein interaction (PPI) network, modules, miRNA hub gene regulatory network and TF hub gene regulatory network was constructed, analyzed and visualized, with which the hub genes miRNAs and TFs nodes were screened out. Finally, validation of hub genes was performed by using receiver operating characteristic curve (ROC) analysis and RT PCR. A total of 948 DEGs were screened out, among which 475 genes were up regulated; while 473 were down regulated. Functional enrichment analyses indicated that DEGs were mainly involved in defense response, ion transport, neutrophil degranulation and neuronal system. The hub genes (CDK1, TOP2A, MAD2L1, RSL24D1, CDKN1A, NOTCH3, MYB, PWP2, WNT7B and HSPA12B) were identified from PPI network, modules, miRNA hub gene regulatory network and TF hub gene regulatory network. We identified a series of key genes along with the pathways that were most closely related with dementia initiation and progression. Our results provide a more detailed molecular mechanism for the advancement of dementia, shedding light on the potential biomarkers and therapeutic targets.

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“…Further studies have shown that IL2RA plays a crucial role in sensitizing T cells to induce cell death (Borysewicz-Sańczyk et al, 2020). Changes in IL2RA expression may affect immune and inflammatory signaling cascade responses, which in turn affect CD4 + T cell differentiation and TReg cell suppressive activity (Asouri et al, 2020). IL2 signaling is involved in the differentiation and homeostasis of regulatory T cells (Tregs), and IL2 signaling is involved in the induction of cell growth and effector T cell proliferation (Zeebroeck et al, 2021).…”

Section: Phaseol May Reduce Inflammatory Cell Activation and Inflamma...mentioning

confidence: 99%

Exploring the mechanism of action of licorice in the treatment of COVID-19 through bioinformatics analysis and molecular dynamics simulation

Cao

Gong²,

Wu³

et al. 2022

Front. Pharmacol.

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Purpose: The rapid worldwide spread of Corona Virus Disease 2019 (COVID-19) has become not only a global challenge, but also a lack of effective clinical treatments. Studies have shown that licorice can significantly improve clinical symptoms such as fever, dry cough and shortness of breath in COVID-19 patients with no significant adverse effects. However, there is still a lack of in-depth analysis of the specific active ingredients of licorice in the treatment of COVID-19 and its mechanism of action. Therefore, we used molecular docking and molecular dynamics to explore the mechanism of action of licorice in the treatment of COVID-19.Methods: We used bioinformatics to screen active pharmaceutical ingredients and potential targets, the disease-core gene target-drug network was established and molecular docking was used for verification. Molecular dynamics simulations were carried out to verify that active ingredients were stably combined with protein targets. The supercomputer platform was used to measure and analyze stability of protein targets at the residue level, solvent accessible surface area, number of hydrogen bonds, radius of gyration and binding free energy.Results: Licorice had 255 gene targets, COVID-19 had 4,628 gene targets, the intersection gene targets were 101. Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene ontology (GO) analysis showed that licorice played an important role mainly through the signaling pathways of inflammatory factors and oxidative stress. Molecular docking showed that Glycyrol, Phaseol and Glyasperin F in licorice may playe a role in treating COVID-19 by acting on STAT3, IL2RA, MMP1, and CXCL8. Molecular dynamics were used to demonstrate and analyze the binding stability of active ingredients to protein targets.Conclusion: This study found that Phaseol in licorice may reduce inflammatory cell activation and inflammatory response by inhibiting the activation of CXCL8 and IL2RA; Glycyrol may regulate cell proliferation and survival by acting on STAT3. Glyasperin F may regulate cell growth by inhibiting the activation of MMP1, thus reducing tissue damage and cell death caused by excessive inflammatory response and promoting the growth of new tissues. Therefore, licorice is proposed as an effective candidate for the treatment of COVID-19 through STAT3, IL2RA, MMP1, and CXCL8.

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Analysis of Single Nucleotide Polymorphisms in HLA-DRA, IL2RA, and HMGB1 Genes in Multiple Sclerosis

Cited by 8 publications

References 20 publications

HLA‐DRA Gene Polymorphisms Are Associated with Graves’ Disease as an Autoimmune Thyroid Disease

HLA‐DRA Gene Polymorphisms Are Associated with Graves’ Disease as an Autoimmune Thyroid Disease

Identification of Key Pathways and Genes in Dementia via Integrated Bioinformatics Analysis

Exploring the mechanism of action of licorice in the treatment of COVID-19 through bioinformatics analysis and molecular dynamics simulation

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