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 (=4.109, 95% 1.990 to 8.486, <0.001). Similarly, the inverse variance weighted (IVW) model showed a positive correlation between C5a and Graves' ophthalmopathy (=2.901, 95% 1.225 to 6.869, =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.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.11817/j.issn.1672-7347.2024.240062 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Complement C5/C5a in the diagnosis and treatment of Graves ophthalmopathy: A Mendelian randomized study.
Zhong Nan Da Xue Xue Bao Yi Xue Ban
October 2024
Department of Ophthalmology, Third Xiangya Hospital, Central South University, Changsha 410013, China.
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.
View Article and Find Full Text PDFAntibodies against the receptor for insulin-like growth factor 1 (IGF-1RAb), insulin-like growth factor 1 (IGF-1), and insulin-like growth factor binding protein 3 (IGFBP-3) in the serum of patients with Graves' and Basedow's disease with and without orbitopathy.
Endokrynol Pol
March 2025
Department of Anaesthesiology and Intensive Therapy, Faculty of Medical Sciences in Zabrze, Medical University of Silesia in Katowice, Poland.
Introduction: Proven risk factors for thyroid orbitopathy (TO) are thyroid dysfunction, smoking, and high levels of thyrotropin receptor antibodies (TRAb), and the role of insulin-like growth factor 1 (IGF-1), the receptor for IGF-1 (IGF-1R), and antibodies to the receptor for IGF-1 (IGF-1RAb) are also debated. IGF-1R is overexpressed in fibroblasts and orbital lymphocytes in TO patients. It forms a functional complex and mediates signal transduction through thyroid stimulating hormone receptor (TSHR).
View Article and Find Full Text PDFQuantifying anterior segment vascular changes in thyroid eye disease using optical coherence tomography angiography.
BMC Med Imaging
March 2025
Ophthalmology Department and Eye Research Center, Farabi Eye Hospital, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.
Purpose: Thyroid eye disease (TED) presents challenges in the accurate assessment of disease activity, especially concerning ocular surface manifestations. This study aims to evaluate the potential of anterior segment optical coherence tomography angiography (AS-OCTA) in quantifying vascular changes associated with TED, thereby enhancing understanding of its pathophysiology and aiding in diagnosis and management.
Methods: We conducted a cross-sectional study involving 29 TED patients and 21 healthy controls.
Development and validation of potential molecular subtypes and signatures of thyroid eye disease based on angiogenesis-related gene analysis.
BMC Pharmacol Toxicol
March 2025
Hunan University of Chinese Medicine, Changsha, Hunan Province, 410208, China.
Background: Thyroid eye disease (TED) is an autoimmune inflammatory disorder of the orbit, associated with a range of potential clinical sequelae. Tumor cells in TED overexpress pro-angiogenic factors, driving the formation of heterogeneous and immature neovascularization. This dysregulated angiogenesis often leads to a hypoxic microenvironment due to insufficient perfusion.
View Article and Find Full Text PDFButyrate Ameliorates Graves' Orbitopathy Through Regulating Orbital Fibroblast Phenotypes and Gut Microbiota.
Invest Ophthalmol Vis Sci
March 2025
Department of Ophthalmology, The Second Xiangya Hospital, Central South University, Changsha, Hunan, China.
Purpose: Graves' orbitopathy (GO), the common extrathyroidal complication of Graves' disease (GD), is characterized by orbital fibroblast stimulation, adipogenesis, and hyaluronan production. Recently, gut microbiota and its metabolites have garnered attention for their possible involvement in GO.
Methods: This study utilized an animal model of GO and examined the effects of butyrate treatment on orbital fibroblast cells and gut microbiota.
Want AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!