Meta-analysis of FOXP3 gene rs3761548 and rs2232365 polymorphism and multiple sclerosis susceptibility

Zhang, Yijian; Zhang, Junxin; Liu, Hao; He, Fan; Chen, Angela Carley; Yang, Huilin; Pi, Bin

doi:10.1097/md.0000000000017224

Cited by 12 publications

(7 citation statements)

References 34 publications

(33 reference statements)

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“…MS is the cause of death in more than 50% of the affected patients (122). Factors involved in the pathogenesis are both environmental and genetic (123)(124)(125)(126)(127)(128)(129)(130)(131). Among the environmental factors, microbes (and their secreted products or toxins) play a critical role in the pathogenesis of MS (132,133).…”

Section: Multiple Sclerosismentioning

confidence: 99%

The Gut-Brain Axis: How Microbiota and Host Inflammasome Influence Brain Physiology and Pathology

2020

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The human microbiota has a fundamental role in host physiology and pathology. Gut microbial alteration, also known as dysbiosis, is a condition associated not only with gastrointestinal disorders but also with diseases affecting other distal organs. Recently it became evident that the intestinal bacteria can affect the central nervous system (CNS) physiology and inflammation. The nervous system and the gastrointestinal tract are communicating through a bidirectional network of signaling pathways called the gut-brain axis, which consists of multiple connections, including the vagus nerve, the immune system, and bacterial metabolites and products. During dysbiosis, these pathways are dysregulated and associated with altered permeability of the blood-brain barrier (BBB) and neuroinflammation. However, numerous mechanisms behind the impact of the gut microbiota in neuro-development and -pathogenesis remain poorly understood. There are several immune pathways involved in CNS homeostasis and inflammation. Among those, the inflammasome pathway has been linked to neuroinflammatory conditions such as multiple sclerosis, Alzheimer’s and Parkinson’s diseases, but also anxiety and depressive-like disorders. The inflammasome complex assembles upon cell activation due to exposure to microbes, danger signals, or stress and lead to the production of pro-inflammatory cytokines (interleukin-1β and interleukin-18) and to pyroptosis. Evidences suggest that there is a reciprocal influence of microbiota and inflammasome activation in the brain. However, how this influence is precisely working is yet to be discovered. Herein, we discuss the status of the knowledge and the open questions in the field focusing on the function of intestinal microbial metabolites or products on CNS cells during healthy and inflammatory conditions, such as multiple sclerosis, Alzheimer’s and Parkinson’s diseases, and also neuropsychiatric disorders. In particular, we focus on the innate inflammasome pathway as immune mechanism that can be involved in several of these conditions, upon exposure to certain microbes.

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Section: Multiple Sclerosismentioning

confidence: 99%

The Gut-Brain Axis: How Microbiota and Host Inflammasome Influence Brain Physiology and Pathology

2020

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“…In 2016, a study of different variants of FOXP3 found a significant difference in the distribution of the rs3761548 and rs2232365 alleles in MS patients compared to controls, suggesting that this polymorphism leads to suppression of FOXP3. 30 The study found that 24% of MS patients who had recently been exposed to a viral disease suggesting that they may be a useful strategy for the treatment of autoimmune diseases. 32 RORC is the major transcription factor for Th17 cells, and its transcription leads to the differentiation of CD 4+ cells into them.…”

Section: Discussionmentioning

confidence: 98%

LncRNA‐miRNA network analysis across the Th17 cell line reveals biomarker potency of lncRNA NEAT1 and KCNQ1OT1 in multiple sclerosis

Karimi

Azari

Tahmasebi

et al. 2022

J Cellular Molecular Medi

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Differentiation of CD4+ T cells into Th17 cells is an important factor in the onset and progression of multiple sclerosis (MS) and Th17/Treg imbalance. Little is known about the role of lncRNAs in the differentiation of CD4+ cells from Th17 cells. This study aimed to analyse the lncRNA‐miRNAs network involved in MS disease and its role in the differentiation of Th17 cells. The lncRNAs in Th17 differentiation were obtained from GSE66261 using the GEO datasets. Differential expression of lncRNAs in Th17 primary cells compared to Th17 effector cells was investigated by RNA‐seq analysis. Next, the most highlighted lncRNAs in autoimmune diseases were downloaded from the lncRNAs disease database, and the most critical miRNA was extracted by literature search. Then, the lncRNA‐miRNA interaction was achieved by the Starbase database, and the ceRNA network was designed by Cytoscape. Finally, using the CytoHubba application, two hub lncRNAs with the most interactions with miRNAs were identified by the MCODE plug‐in. The expression level of genes was measured by qPCR, and the plasma level of cytokines was analysed by ELISA kits. The results showed an increase in the expression of NEAT1, KCNQ1OT1 and RORC and a decrease in the expression of FOXP3. In plasma, an upregulation of IL17 and a downregulation of TGFB inflammatory cytokines were detected. The dysregulated expression of these genes could be attributed to relapsing‐remitting MS (RR‐MS) patients and help us understand MS pathogenesis better.

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“…Flauzino et al found an association between the rs3761548 FOXP3 and MS in females in a Brazilian population [ 46 ]. Additionally, Zhang et al [ 47 ] performed a meta-analysis on five studies investigating the correlation between FOXP3 polymorphisms and MS risk. Authors showed that the rs3761548 could be associated with MS susceptibility, especially in Asians.…”

Section: Discussionmentioning

confidence: 99%

FOXP3 and GATA3 Polymorphisms, Vitamin D3 and Multiple Sclerosis

et al. 2021

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Background: Regulatory T cells (Tregs) alterations have been implicated in the pathogenesis of Multiple Sclerosis (MS). Recently, a crucial role of the X-Linked Forkhead Box P3 (FoxP3) for the development and the stability of Tregs has emerged, and FOXP3 gene polymorphisms have been associated with the susceptibility to autoimmune diseases. The expression of Foxp3 in Tregs is regulated by the transcription factor GATA binding-protein 3 (GATA3) and vitamin D3. The aim of this retrospective case-control study was to investigate the potential association between FOXP3 and GATA3 genetic variants, Vitamin D3, and MS risk. Methods: We analyzed two polymorphisms in the FOXP3 gene (rs3761547 and rs3761548) and a polymorphism in the GATA3 gene (rs3824662) in 106 MS patients and 113 healthy controls. Serum 25(OH)D3 was also measured in all participants. Results: No statistically significant genotypic and allelic differences were found in the distribution of FOXP3 rs3761547 and rs3761548, or GATA3 rs3824662 in the MS patients, compared with controls. Patients that were homozygous for rs3761547 had lower 25(OH)D3 levels. Conclusions: Our findings did not show any association among FOXP3 and GATA3 SNPs, vitamin D3, and MS susceptibility.

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Meta-analysis of FOXP3 gene rs3761548 and rs2232365 polymorphism and multiple sclerosis susceptibility

Cited by 12 publications

References 34 publications

The Gut-Brain Axis: How Microbiota and Host Inflammasome Influence Brain Physiology and Pathology

The Gut-Brain Axis: How Microbiota and Host Inflammasome Influence Brain Physiology and Pathology

LncRNA‐miRNA network analysis across the Th17 cell line reveals biomarker potency of lncRNA NEAT1 and KCNQ1OT1 in multiple sclerosis

FOXP3 and GATA3 Polymorphisms, Vitamin D3 and Multiple Sclerosis

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