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ORIGINAL RESEARCH article

Front. Cardiovasc. Med.
Sec. Cardiovascular Metabolism
Volume 11 - 2024 | doi: 10.3389/fcvm.2024.1410006

Serum Metabolites and Hypercholesterolemia: Insights from a Two-Sample Mendelian Randomization Study

Provisionally accepted
Weitao Wang Weitao Wang 1*Jingwen Qiao Jingwen Qiao 2Zhaoyin Su Zhaoyin Su 1晖 韦 晖 韦 3Jincan Wu Jincan Wu 4Yatao Liu Yatao Liu 1Rubing Lin Rubing Lin 5Su Zhaoyin Su Zhaoyin 6
  • 1 First Hospital of Lanzhou University, Lanzhou, China
  • 2 Shanxi Medical University, Taiyuan, Shanxi Province, China
  • 3 School of Stomatology, Lanzhou University, Lanzhou, Gansu Province, China
  • 4 The Second Affiliated Hospital, Fujian University of Traditional Chinese Medicine, Fuzhou, Fujian Province, China
  • 5 Shenzhen Children's Hospital, Shenzhen, Guangdong Province, China
  • 6 Department of Trauma Surgery, University Medical Center Regensburg, Regensburg, Bavaria, Germany

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

    Background Hypercholesterolemia, a major risk factor for cardiovascular diseases, lacks a comprehensive understanding of its association with serum metabolites in the pathogenesis. Methods This study employed genome-wide association study (GWAS) data to explore the relationship between serum metabolites and hypercholesterolemia, identifying significant metabolites through Mendelian Randomization (MR) and KEGG pathway enrichment analysis. Data on metabolites were sourced from a European population, with analysis focusing on individuals diagnosed with hypercholesterolemia. Results Out of 486 metabolites analyzed, ten showed significant associations with hypercholesterolemia, categorized into those enhancing risk and those with protective effects. Specifically, 2-methoxyacetaminophen sulfate and 1-oleoylglycerol (1-monoolein) were identified as risk-enhancing, with odds ratios (OR) of 1.545 (95% Confidence Interval [CI]: 1.230-1.939; P_FDR = 3E-04) and 1.462 (95% CI: 1.036-2.063; P_FDR = 0.037), respectively. On the protective side, 3-(cystein-S-yl)acetaminophen, hydroquinone sulfate, and 2-hydroxyacetaminophen sulfate demonstrated ORs of 0.793 (95% CI: 0.735-0.856; P_FDR = 6.18E-09), 0.641 (95% CI: 0.423-0.971; P_FDR = 0.042), and 0.607 (95% CI: 0.541-0.681; P_FDR = 5.39E-17), respectively. In addition, KEGG pathway enrichment analysis further revealed eight important pathways, including "biosynthesis of valine, leucine, and isoleucine", "phenylalanine metabolism", and "pyruvate metabolism", emphasizing their significant role in the pathogenesis of hypercholesterolemia. Conclusion This study highlights the potential causal relationship between specific serum metabolites and hypercholesterolemia, providing new insights into the metabolic underpinnings of the disease. The identified metabolites and pathways offer promising targets for therapeutic intervention and warrant further investigation.

    Keywords: Mendelian randomization, causality, Hypercholesterolemia, Metabolites, Treatment

    Received: 31 Mar 2024; Accepted: 12 Jul 2024.

    Copyright: © 2024 Wang, Qiao, Su, 韦, Wu, Liu, Lin and Zhaoyin. 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: Weitao Wang, First Hospital of Lanzhou University, Lanzhou, 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.