Unveiling the role of lipid metabolism in haemorrhagic disorders: genetic insights and therapeutic perspectives.

IF 2.6 4区 医学 Q2 HEMATOLOGY
Jiaqi Wei, Zhen Yang, Xiaojin Wu, Nana Zheng, Depei Wu
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引用次数: 0

Abstract

Background: Coagulation defects, including purpura and other haemorrhagic conditions, are a critical area of medical research because of their significant health effects worldwide. Understanding the metabolic basis of these conditions may improve therapeutic strategies.

Methods: A two-sample Mendelian randomization (MR) approach was employed to evaluate the causal relationships between the levels of 1,400 metabolites and coagulation defects. Colocalization analysis confirmed significant shared genetic influences. Pathway and protein‒protein interaction (PPI) analyses identified rate-limiting enzymes and drug targets. The impacts of lifestyle factors on metabolite levels were also explored through MR.

Results: MR analysis revealed four metabolites whose abundance was significantly associated with coagulation defects: docosapentaenoate n3 DPA 22:5n3 (DPA) (OR: 1.594, 95% CI: 1.263-2.011, P < 0.001), 1-palmitoyl-2-stearoyl-gpc (PSPC) (16:0/18:0) (OR: 1.294, 95% CI: 1.134-1.477, P < 0.001), 1-stearoyl-2-docosahexaenoyl-gpc (SDPC) (18:0/22:6) (OR: 1.232, 95% CI: 1.101-1.380, P < 0.001) and hydroxypalmitoyl sphingomyelin (HPSM) (d18:1/16:0 (OH)) (OR: 0.803, 95% CI: 0.719-0.896, P < 0.001). Colocalization analysis provided robust evidence for shared genetic loci. Pathway analysis highlighted the importance of lipid metabolism, identifying key enzymes such as FADS1, FADS2 and TCP1. PPI analysis revealed an interaction between TCP1 and plasminogen, indicating potential therapeutic synergy. Further analysis revealed that lifestyle factors, including dried fruit and oily fish intake, were linked to the abundance of metabolites associated with coagulation risk.

Conclusions: This study identifies specific metabolites and metabolic pathways involved in coagulation defects, proposes novel therapeutic targets and highlights the roles of dietary and lifestyle interventions in the management of these conditions. These findings pave the way for personalized strategies to manage coagulation-related conditions.

揭示出血性疾病中脂质代谢的作用:遗传见解和治疗观点。
背景:凝血缺陷,包括紫癜和其他出血性疾病,是医学研究的一个重要领域,因为它们对全世界的健康有重大影响。了解这些疾病的代谢基础可以改善治疗策略。方法:采用双样本孟德尔随机化(MR)方法评估1400种代谢物水平与凝血缺陷之间的因果关系。共定位分析证实了显著的共同遗传影响。途径和蛋白-蛋白相互作用(PPI)分析确定了限速酶和药物靶点。结果:MR分析显示四种代谢物的丰富度与凝血缺陷显著相关:docosapentaenoate n3 DPA 22:5n3 (DPA) (OR: 1.594, 95% CI: 1.263-2.011, P)。本研究确定了与凝血缺陷相关的特定代谢物和代谢途径,提出了新的治疗靶点,并强调了饮食和生活方式干预在这些疾病管理中的作用。这些发现为管理凝血相关疾病的个性化策略铺平了道路。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Thrombosis Journal
Thrombosis Journal Medicine-Hematology
CiteScore
3.80
自引率
3.20%
发文量
69
审稿时长
16 weeks
期刊介绍: Thrombosis Journal is an open-access journal that publishes original articles on aspects of clinical and basic research, new methodology, case reports and reviews in the areas of thrombosis. Topics of particular interest include the diagnosis of arterial and venous thrombosis, new antithrombotic treatments, new developments in the understanding, diagnosis and treatments of atherosclerotic vessel disease, relations between haemostasis and vascular disease, hypertension, diabetes, immunology and obesity.
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