Associations of the circulating levels of cytokines with risk of ankylosing spondylitis: a Mendelian randomization study

Yang Ye; Chuan-En Wang; Rui Zhong; Xiao-Ming Xiong

doi:10.3389/fimmu.2023.1291206

Associations of the circulating levels of cytokines with risk of ankylosing spondylitis: a Mendelian randomization study

Front Immunol. 2023 Dec 20:14:1291206. doi: 10.3389/fimmu.2023.1291206. eCollection 2023.

Authors

Yang Ye¹, Chuan-En Wang¹, Rui Zhong¹, Xiao-Ming Xiong¹

Affiliation

¹ Department of Spinal Surgery, Affiliated Sports Hospital of Chengdu Sport University, Chengdu, Sichuan, China.

Abstract

Background: Observational studies have shown that changes in circulating cytokine/growth factor levels occur throughout the initiation and progression of ankylosing spondylitis (AS), yet whether they are etiologic or downstream effects remains unclear. In this study, we performed a summarized-level bidirectional Mendelian randomization (MR) analysis to shed light on the causal relationship between the two.

Methods: Genetic instrumental-variables (IVs) associated with circulating cytokine/growth factor levels were derived from a genome-wide association study (GWAS) of 8,293 European individuals, whereas summary data for the AS were obtained from a FinnGen GWAS of 166,144 participants. We used the inverse-variance-weighted (IVW) method as the main analysis for causal inference. Furthermore, several sensitivity analyses (MR-Egger, weighted median, MR-PRESSO and Cochran's Q test) were utilized to examine the robustness of the results. Finally, reverse MR analysis was performed to assess reverse causality between AS and circulating cytokine/growth factor levels.

Results: After Bonferroni correction, circulating levels of Cutaneous T-cell attracting (CTACK) and Monocyte specific chemokine 3 (MCP-3) were positively associated with a higher risk of AS (odds ratio [OR]: 1.224, 95% confidence interval [95% Cl]: 1.022 ~ 1.468, P = 0.028; OR: 1.250, 95% Cl: 1.016 ~ 1.539, P = 0.035). In addition, elevated circulating levels of Basic fibroblast growth factor (FGF-basic), Granulocyte colony-stimulating factor (G-CSF) and MCP-3 was considered a consequence of AS disease (β = 0.023, P = 0.017; β = 0.017, P = 0.025; β = 0.053, P = 0.025). The results of the sensitivity analysis were generally consistent.

Conclusion: The present study supplies genetic evidence for the relationship between circulating cytokine levels and AS. Targeted interventions of specific cytokines may help to reduce the risk of AS initiation and progression.

Keywords: CTACK; FGF-basic; G-CSF; MCP-3; Mendelian randomization; ankylosing spondylitis; causal effect; cytokines.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Cytokines*
Genome-Wide Association Study
Granulocyte Colony-Stimulating Factor
Humans
Mendelian Randomization Analysis
Spondylitis, Ankylosing* / genetics

Substances

Cytokines
Granulocyte Colony-Stimulating Factor

Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. This work was supported by grants from the Bethune Charitable Foundation (NO: BK-JP2020005).