补体C4位点的拷贝数变异与多发性硬化症的风险相关。

IF 5 2区医学 Q1 CLINICAL NEUROLOGY

Multiple Sclerosis Journal Pub Date : 2025-09-01 Epub Date: 2025-03-15 DOI:10.1177/13524585251324850

Jacqueline Williams, Wesley M Marin, Kristen J Wade, Rayo Suseno, Kerry Kizer, Stacy Caillier, Danillo G Augusto, Paul J Norman, Jill A Hollenbach

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引用次数: 0

摘要

背景：由于在多发性硬化症病变中存在补体激活产物，补体系统被怀疑在多发性硬化症（MS）中起作用。目的：我们试图了解补体成分4 （C4）基因的变异是否与多发性硬化症有关。方法：在这里，我们使用新一代测序和我们的新型生物信息学工具C4Investigator来询问多发性硬化症中C4拷贝数的变异。结果：我们发现，与欧洲血统的多发性硬化症患者相比，对照组中C4的总拷贝数更高(p < 10-16，优势比（OR) = 0.43, 95%可信区间（CI）： 0.37-0.49）。结论：这一发现表明，较低的C4拷贝增加了MS的风险，类似于在其他自身免疫性疾病中所见的关联。

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Copy number variation at the complement C4 locus is associated with risk for multiple sclerosis.

Background: The complement system has been suspected to play a role in multiple sclerosis (MS) due to presence of complement activation products in MS lesions.

Objective: We sought to understand whether variation in the complement component 4 (C4) gene is associated with MS.

Methods: Here we used next-generation sequencing and our novel bioinformatics tool, C4Investigator, to interrogate C4 copy number variation in MS.

Results: We found higher overall copy number of C4 in controls (p < 10^-16, odds ratio (OR) = 0.43, 95% confidence interval (CI): 0.37-0.49) compared to MS patients with European ancestry.

Conclusion: This finding suggests that lower C4 copies confer risk for MS, similar to associations seen in other autoimmune disorders.

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来源期刊

Multiple Sclerosis Journal 医学-临床神经学

CiteScore

10.90

自引率

6.90%

发文量

186

审稿时长

3-8 weeks

期刊介绍： Multiple Sclerosis Journal is a peer-reviewed international journal that focuses on all aspects of multiple sclerosis, neuromyelitis optica and other related autoimmune diseases of the central nervous system. The journal for your research in the following areas: * __Biologic basis:__ pathology, myelin biology, pathophysiology of the blood/brain barrier, axo-glial pathobiology, remyelination, virology and microbiome, immunology, proteomics * __Epidemology and genetics:__ genetics epigenetics, epidemiology * __Clinical and Neuroimaging:__ clinical neurology, biomarkers, neuroimaging and clinical outcome measures * __Therapeutics and rehabilitation:__ therapeutics, rehabilitation, psychology, neuroplasticity, neuroprotection, and systematic management Print ISSN: 1352-4585