Skip to main content

ORIGINAL RESEARCH article

Front. Immunol.
Sec. Cytokines and Soluble Mediators in Immunity
Volume 15 - 2024 | doi: 10.3389/fimmu.2024.1445790
This article is part of the Research Topic Inflammation and Immune Factors in Venous Thromboembolism View all 3 articles

Potential Causal Relationships Between Blood Metabolites, Inflammatory Cytokines, and Venous Thromboembolism

Provisionally accepted
Qianying Liu Qianying Liu Fangfang Lu Fangfang Lu *Fan Yang Fan Yang Kangli Kong Kangli Kong
  • Nanjing Jiangning Hospital, Nanjing, China

The final, formatted version of the article will be published soon.

    Background Venous thromboembolism (VTE) is the abnormal coagulation of blood in deep veins, which impairs venous return and includes deep vein thrombosis (DVT) and pulmonary embolism (PE). The incidence of VTE is increasing, leading to severe complications and sequelae. Despite the widespread application of multi-omics analyses in vascular disease research, identifying the specific links between various metabolic products, cytokines, and VTE, as well as their potential mediating roles, requires further validation due to confounding factors.Methods Summary statistics for 1,091 metabolites, 309 metabolite ratios (8,299 individuals), and 41 cytokines and growth factors (8,293 individuals) were obtained from the largest genome-wide association studies (GWAS).Summary statistics for VTE (21,021 cases, 391,160 controls), DVT (6,501 cases, 357,111 controls), and PE (10,046 cases, 401,128 controls) were derived from the FinnGen R10 dataset. We initially examined causal relationships using two-sample MR analysis, followed by Two-step Mendelian Randomization (TSMR) and Multivariable Mendelian Randomization (MVMR) to identify potential mediating mechanisms.We identified causal associations for 78 blood metabolites with VTE, 79 with DVT, and 81 with PE. Among all 41 inflammatory cytokines included, only platelet-derived growth factor BB (PDGF-BB) levels showed a causal relationship with increased risks of VTE, DVT, and PE. MVMR analysis revealed that glycocholate levels' associations with VTE, DVT, and PE were mediated by PDGF-BB, accounting for 14.54% (p=2.84E-04), 17.10% (p=3.64E-05), and 10.44% (p=1.39E-02), respectively. Furthermore, dodecanedioate (C12:1-DC) levels associations with VTE and DVT were also mediated by PDGF-BB, accounting for 12.79% (p=6.10E-04) and 12.17% (p=2.13E-04), respectively.This study reveals significant associations between specific blood metabolites and the risks of VTE, DVT, and PE, with some associations potentially mediated by PDGF-BB.

    Keywords: Metabolites, inflammatory cytokines, Venous Thromboembolism, Mendelian Randomization Analysis, deep vein thrombosis, Pulmonary Embolism

    Received: 08 Jun 2024; Accepted: 05 Sep 2024.

    Copyright: © 2024 Liu, Lu, Yang and Kong. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence: Fangfang Lu, Nanjing Jiangning Hospital, Nanjing, China

    Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.