Complement C5/C5a in the diagnosis and treatment of Graves' ophthalmopathy: A Mendelian randomized study.

Q3 Medicine

中南大学学报(医学版) Pub Date : 2024-10-28 DOI:10.11817/j.issn.1672-7347.2024.240062

Min Zhu, Bingxuan Wu, Changci Chen-Zhao, Haiyan Chen, Wei Xiong

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引用次数: 0

Abstract

Objectives: Graves' ophthalmopathy is a complex organ-specific autoimmune disease with an unclear pathogenesis. Complement component 5/5a (C5/C5a), a key element of the component system, may play a significant role in the disease's pathological process. This study aims to investigate the causal relationship between C5/C5a and Graves' ophthalmopathy using Mendelian randomization (MR) to provide new theoretical insights for its diagnosis and treatment.

Methods: Utilizing summary data from genome-wide association study (GWAS), C5/C5a was designated as the exposure factor and Graves' ophthalmopathy as the outcome. The causal relationship between C5/C5a and Graves' ophthalmopathy was analyzed, and colocalization analysis was performed to determine the posterior probability of hypothesis (PPH) and verify the genetic association between C5 and Graves' ophthalmopathy.

Results: The Wald ratio model showed a significant positive correlation between C5 and Graves' ophthalmopathy (OR=4.109, 95% CI 1.990 to 8.486, P<0.001). Similarly, the inverse variance weighted (IVW) model showed a positive correlation between C5a and Graves' ophthalmopathy (OR=2.901, 95% CI 1.225 to 6.869, P=0.015). Colocalization analysis showed that C5 and Graves' ophthalmopathy share a single nucleotide polymorphism (SNP), rs7036980, within the specified genetic window, with a PPH4 value of 0.81 (a value >0.80 indicates high probability).

Conclusions: Elevated levels of C5/C5a significantly increase the risk of developing Graves' ophthalmopathy. Targeting complement C5 with inhibitors may effectively reduce the risk of Graves' ophthalmopathy.

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补体C5/C5a在Graves眼病诊断和治疗中的作用：一项孟德尔随机研究

目的：Graves眼病是一种复杂的器官特异性自身免疫性疾病，发病机制尚不清楚。补体组分5/5a （C5/C5a）是该组分系统的关键元件，可能在疾病的病理过程中发挥重要作用。本研究旨在运用孟德尔随机化（Mendelian randomization， MR）方法探讨C5/C5a与Graves眼病的因果关系，为Graves眼病的诊断和治疗提供新的理论见解。方法：利用全基因组关联研究（GWAS）的汇总数据，确定C5/C5a为暴露因子，Graves眼病为结局。分析C5/C5a与Graves眼病的因果关系，并进行共定位分析，确定假设的后验概率（PPH），验证C5与Graves眼病的遗传关联。结果：Wald比值模型显示C5与Graves眼病呈正相关（OR=4.109, 95% CI 1.990 ~ 8.486； POR=2.901, 95% CI 1.225 ~ 6.869， P=0.015）。共定位分析显示，C5与Graves眼病在指定遗传窗口内共有一个单核苷酸多态性（SNP） rs7036980， PPH4值为0.81（>0.80为高概率）。结论：C5/C5a水平升高可显著增加Graves眼病的发生风险。用抑制剂靶向补体C5可有效降低Graves眼病的风险。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

中南大学学报(医学版) Medicine-Medicine (all)

CiteScore

1.00

自引率

0.00%

发文量

8237

期刊介绍： Journal of Central South University (Medical Sciences), founded in 1958, is a comprehensive academic journal of medicine and health sponsored by the Ministry of Education and Central South University. The journal has been included in many important databases and authoritative abstract journals at home and abroad, such as the American Medline, Pubmed and its Index Medicus (IM), the Netherlands Medical Abstracts (EM), the American Chemical Abstracts (CA), the WHO Western Pacific Region Medical Index (WPRIM), and the Chinese Science Citation Database (Core Database) (CSCD); it is a statistical source journal of Chinese scientific and technological papers, a Chinese core journal, and a "double-effect" journal of the Chinese Journal Matrix; it is the "2nd, 3rd, and 4th China University Excellent Science and Technology Journal", "2008 China Excellent Science and Technology Journal", "RCCSE China Authoritative Academic Journal (A+)" and Hunan Province's "Top Ten Science and Technology Journals". The purpose of the journal is to reflect the new achievements, new technologies, and new experiences in medical research, medical treatment, and teaching, report new medical trends at home and abroad, promote academic exchanges, improve academic standards, and promote scientific and technological progress.