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多发性硬化症中共存眼部疾病的遗传易感性和因果途径分析。

Genetic susceptibility and causal pathway analysis of eye disorders coexisting in multiple sclerosis.

作者信息

Qiu Xuecheng, Huang Mi Ni, Ping Suning

机构信息

Jiangsu Key Laboratory of Brain Disease Bioinformation, Research Center for Biochemistry and Molecular Biology, Xuzhou Medical University, Xuzhou, Jiangsu, China.

Molecular Cancer Research Center, School of Medicine, Shenzhen Campus of Sun Yat-Sen University, Shenzhen, Guangdong, China.

出版信息

Front Immunol. 2024 Feb 5;15:1337528. doi: 10.3389/fimmu.2024.1337528. eCollection 2024.

Abstract

INTRODUCTION

The comorbidity of optic neuritis with multiple sclerosis has been well recognized. However, the causal association between multiple sclerosis and optic neuritis, as well as other eye disorders, remains incompletely understood. To address these gaps, we investigated the genetically relationship between multiple sclerosis and eye disorders, and explored potential drugs.

METHODS

In order to elucidate the genetic susceptibility and causal links between multiple sclerosis and eye disorders, we performed two-sample Mendelian randomization analyses to examine the causality between multiple sclerosis and eye disorders. Additionally, causal single-nucleotide polymorphisms were annotated and searched for expression quantitative trait loci data. Pathway enrichment analysis was performed to identify the possible mechanisms responsible for the eye disorders coexisting with multiple sclerosis. Potential therapeutic chemicals were also explored using the Cytoscape.

RESULTS

Mendelian randomization analysis revealed that multiple sclerosis increased the incidence of optic neuritis while reducing the likelihood of concurrent of cataract and macular degeneration. Gene Ontology enrichment analysis implicated that lymphocyte proliferation, activation and antigen processing as potential contributors to the pathogenesis of eye disorders coexisting with multiple sclerosis. Furthermore, pharmaceutical agents traditionally employed for allograft rejection exhibited promising therapeutic potential for the eye disorders coexisting with multiple sclerosis.

DISCUSSION

Multiple sclerosis genetically contributes to the development of optic neuritis while mitigating the concurrent occurrence of cataract and macular degeneration. Further research is needed to validate these findings and explore additional mechanisms underlying the comorbidity of multiple sclerosis and eye disorders.

摘要

引言

视神经炎与多发性硬化症的合并症已得到充分认识。然而,多发性硬化症与视神经炎以及其他眼部疾病之间的因果关系仍未完全明了。为填补这些空白,我们研究了多发性硬化症与眼部疾病之间的遗传关系,并探索了潜在药物。

方法

为阐明多发性硬化症与眼部疾病之间的遗传易感性和因果联系,我们进行了两样本孟德尔随机化分析,以检验多发性硬化症与眼部疾病之间的因果关系。此外,对因果单核苷酸多态性进行注释,并搜索表达数量性状位点数据。进行通路富集分析,以确定与多发性硬化症共存的眼部疾病的可能机制。还使用Cytoscape探索了潜在的治疗化学物质。

结果

孟德尔随机化分析显示,多发性硬化症增加了视神经炎的发病率,同时降低了白内障和黄斑变性并发的可能性。基因本体富集分析表明,淋巴细胞增殖、激活和抗原加工是与多发性硬化症共存的眼部疾病发病机制的潜在因素。此外,传统上用于同种异体移植排斥反应的药物制剂对与多发性硬化症共存的眼部疾病显示出有前景的治疗潜力。

讨论

多发性硬化症在遗传上促进了视神经炎的发展,同时减轻了白内障和黄斑变性的并发。需要进一步研究来验证这些发现,并探索多发性硬化症与眼部疾病合并症的其他潜在机制。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7672/10875133/e0c5e80aeb1b/fimmu-15-1337528-g001.jpg

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