| Title: | The Mediating Effect of Inflammatory Biomarkers in the Associations Between Sarcoidosis and Incident Ischemic Stroke: A Prospective Cohort Study |
| Journal: | Brain and Behavior |
| Published: | 26 Mar 2026 |
| Pubmed: | https://pubmed.ncbi.nlm.nih.gov/41888069/ |
| DOI: | https://doi.org/10.1002/brb3.71350 |
Publication 18191
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Abstract
BACKGROUND AND OBJECTIVE: Sarcoidosis, characterized by granulomatous inflammation across multiple systems, has an unclear connection with ischemic stroke and shared molecular pathways. This study explores the link between sarcoidosis and ischemic stroke, focusing on the role of inflammatory markers using large population datasets and multi-omics approaches.</p>
METHODS: Data from 452,382 UK Biobank participants, followed for an average of 13.8 years, were combined with transcriptomic profiles from the GEO database (GSE58294 and GSE19314). A multivariable Cox regression was used to assess the association between sarcoidosis and ischemic stroke. Mediation analysis evaluated the role of inflammatory markers. Differential gene expression, GO and KEGG pathway enrichment, and protein-protein interaction networks were analyzed to explore shared molecular frameworks.</p>
RESULTS: Sarcoidosis (n = 1760 cases) was found to independently increase the risk of ischemic stroke (HR = 1.335, 95% CI: 1.002-1.779). Sensitivity analysis using propensity score matching yielded consistent effect estimates (HR = 1.37). Mediation analysis identified the systemic immune-inflammation index (SII, 8.43%), lymphocyte percentage (7.38%), and C-reactive protein (CRP, 2.17%) as significant intermediaries. Transcriptomic analysis identified three genes-ANKRD22, FCGR1A, and NOG-with differential expression in both conditions, highlighting the TGF-β/BMP signaling pathway and immune regulatory network as shared molecular underpinnings.</p>
CONCLUSION: This study provides the first evidence of a significant association between sarcoidosis and ischemic stroke in a large cohort. By integrating analytical methods, it highlights the role of inflammatory factors and potential molecular interactions between immune and developmental pathways, offering new insights for stroke risk reduction in sarcoidosis patients.</p>
14 Keywords
- Aged
- Biomarkers
- Cohort Studies
- Female
- Humans
- Inflammation
- Ischemic Stroke
- Male
- Middle Aged
- Prospective Studies
- Risk Factors
- Sarcoidosis
- Transcriptome
- United Kingdom
8 Authors
- Zihong Bai
- Wenming Shao
- Xiaxuan Huang
- Shanyuan Tan
- Yitong Ling
- Shiqi Yuan
- Xinya Li
- Jun Lyu
1 Application
| Application ID | Title |
|---|---|
| 104830 | A Study of influencing factors for cerebrovascular and neurodegenerative diseases |
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