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

IF 5 2区医学 Q1 HEMATOLOGY Thrombosis and haemostasis Pub Date : 2024-05-24 DOI:10.1055/s-0044-1786809

Bihui Zhang, Rui He, Ziping Yao, Pengyu Li, Guochen Niu, Ziguang Yan, Yinghua Zou, Xiaoqiang Tong, Min Yang

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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.

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探索循环炎症蛋白与血栓闭塞性脉管炎之间的因果关系：孟德尔随机化研究

背景：血栓闭塞性脉管炎（TAO血栓闭塞性脉管炎（TAO）是一种预后不良、病因不明的血管疾病。本研究采用孟德尔随机分析法（MR）研究循环炎症蛋白对血栓闭塞性脉管炎的因果影响：在这项MR分析中，来自91种炎症相关蛋白的全基因组关联研究荟萃分析的汇总统计数据与FinnGen联盟R10版本中独立来源的TAO数据进行了整合。采用的方法包括反方差加权法、MR-Egger回归法、加权中值法、MR-PRESSO和多变量MR（MVMR）分析：分析表明，C-C 矩阵趋化因子 4 水平越高，患 TAO 的风险就越低，几率比（OR）为 0.44（95% 置信区间[CI]：0.29-0.67；P = 1.4 × 10-4；调整后 P = 0.013）。同样，神经胶质细胞系源性神经营养因子对TAO也有提示性保护作用（OR：0.43，95% CI：0.22-0.81；P = 0.010；调整后P = 0.218）。相反，C-C 矩阵趋化因子 23 水平越高，TAO 风险越高（OR：1.88，95% CI：1.21-2.93；p = 0.005；调整后 p = 0.218）。敏感性分析和 MVMR 没有发现异质性或多义性的证据：本研究发现 C-C motif 趋化因子 4 和胶质细胞系衍生神经营养因子是 TAO 的潜在保护性生物标志物，而 C-C motif 趋化因子 23 则是一个提示性风险标志物。这些发现阐明了潜在的因果关系，并强调了这些蛋白质在 TAO 发病机制和前瞻性治疗策略中的重要作用。

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来源期刊

Thrombosis and haemostasis 医学-外周血管病

CiteScore

11.90

自引率

9.00%

发文量

140

审稿时长

1 months

期刊介绍： Thrombosis and Haemostasis publishes reports on basic, translational and clinical research dedicated to novel results and highest quality in any area of thrombosis and haemostasis, vascular biology and medicine, inflammation and infection, platelet and leukocyte biology, from genetic, molecular & cellular studies, diagnostic, therapeutic & preventative studies to high-level translational and clinical research. The journal provides position and guideline papers, state-of-the-art papers, expert analysis and commentaries, and dedicated theme issues covering recent developments and key topics in the field.