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CC BY-NC-ND 4.0 · Thromb Haemost
DOI: 10.1055/s-0044-1786809
Atherosclerosis and Ischaemic Disease

Exploring Causal Relationships between Circulating Inflammatory Proteins and Thromboangiitis Obliterans: A Mendelian Randomization Study

Bihui Zhang    *
1   Department of Interventional Radiology and Vascular Surgery, Peking University First Hospital, Beijing, China
,
Rui He   *
2   Department of Plastic Surgery and Burn, Peking University First Hospital, Beijing, China
,
Ziping Yao   *
1   Department of Interventional Radiology and Vascular Surgery, Peking University First Hospital, Beijing, China
,
Pengyu Li
1   Department of Interventional Radiology and Vascular Surgery, Peking University First Hospital, Beijing, China
,
Guochen Niu
1   Department of Interventional Radiology and Vascular Surgery, Peking University First Hospital, Beijing, China
,
Ziguang Yan
1   Department of Interventional Radiology and Vascular Surgery, Peking University First Hospital, Beijing, China
,
Yinghua Zou
1   Department of Interventional Radiology and Vascular Surgery, Peking University First Hospital, Beijing, China
,
Xiaoqiang Tong
1   Department of Interventional Radiology and Vascular Surgery, Peking University First Hospital, Beijing, China
,
Min Yang
1   Department of Interventional Radiology and Vascular Surgery, Peking University First Hospital, Beijing, China
› Author Affiliations Funding This research was funded by National High Level Hospital Clinical Research Funding (Interdepartmental Research Project of Peking University First Hospital) 2023IR32, the National Natural Science Foundation of China (82200537), and the Interdisciplinary Clinical Research Project of Peking University First Hospital, grant No. 2018CR33. The APC was funded by Peking University First Hospital.
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Abstract

Background Thromboangiitis obliterans (TAO) is a vascular condition characterized by poor prognosis and an unclear etiology. This study employs Mendelian randomization (MR) to investigate the causal impact of circulating inflammatory proteins on TAO.

Methods In this MR analysis, summary statistics from a genome-wide association study meta-analysis of 91 inflammation-related proteins were integrated with independently sourced TAO data from the FinnGen consortium's R10 release. Methods such as inverse variance weighting, MR–Egger regression, weighted median approaches, MR-PRESSO, and multivariable MR (MVMR) analysis were utilized.

Results The analysis indicated an association between higher levels of C–C motif chemokine 4 and a reduced risk of TAO, with an odds ratio (OR) of 0.44 (95% confidence interval [CI]: 0.29–0.67; p = 1.4 × 10−4; adjusted p = 0.013). Similarly, glial cell line-derived neurotrophic factor exhibited a suggestively protective effect against TAO (OR: 0.43, 95% CI: 0.22–0.81; p = 0.010; adjusted p = 0.218). Conversely, higher levels of C–C motif chemokine 23 were suggestively linked to an increased risk of TAO (OR: 1.88, 95% CI: 1.21–2.93; p = 0.005; adjusted p = 0.218). The sensitivity analysis and MVMR revealed no evidence of heterogeneity or pleiotropy.

Conclusion This study identifies C–C motif chemokine 4 and glial cell line-derived neurotrophic factor as potential protective biomarkers for TAO, whereas C–C motif chemokine 23 emerges as a suggestive risk marker. These findings elucidate potential causal relationships and highlight the significance of these proteins in the pathogenesis and prospective therapeutic strategies for TAO.

Keywords

thromboangiitis obliterans - Mendelian randomization - inflammatory proteins - biomarkers - therapeutic target

Data Availability Statement

The datasets analyzed during the current study are available in the EBI GWAS Catalog (accession numbers GCST90274758 to GCST90274848 and GCST90029014), https://www.ebi.ac.uk/gwas/, and the FinnGen repository (finngen_R10_I9_THROMBANG), https://www.finngen.fi/en/access_results.


Ethical Approval Statement

This research has been conducted using published studies and consortia providing publicly available summary statistics. All original studies have been approved by the corresponding ethical review board, and the participants have provided informed consent. In addition, no individual-level data were used in this study. Therefore, no new ethical review board approval was required


Authors' Contribution

Conception and design: M.Y. and B.Z. Administrative support: X.T. and Y.Z. Provision of study materials or patients: Z.Y. and G.N. Collection and assembly of data: B.Z., Z.Y., and R.H. Data analysis and interpretation: B.Z., R.H., and Z.Y. Manuscript writing: All authors. Final approval of manuscript: All authors.


* These authors equally contributed to this paper and thus shared the co-first authorship.


Supplementary Material



Publication History

Received: 07 December 2023

Accepted: 05 April 2024

Article published online:
24 May 2024

© 2024. The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/)

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