Zeng Xingdu, Zhong Bin
Department of Respiratory Medicine, The First Affiliated Hospital of Gannan Medical University, Ganzhou, Jiangxi, China.
Front Cardiovasc Med. 2024 Oct 15;11:1304986. doi: 10.3389/fcvm.2024.1304986. eCollection 2024.
Several recent investigations have posited that distinct metabolites in the bloodstream may be correlated with the pathogenesis of Pulmonary Hypertension (PH). Nonetheless, the interrelationship between the pathogenesis of PH and metabolite fluctuations remains incompletely elucidated, and findings may differ across studies.
In the extant research, data from 486 metabolite-and PH-related genetic variants in human subjects were procured based on Genome-Wide Association Studies (GWAS) and Finnish databases. Univariate Mendelian Randomization analyses were deployed to evaluate the causal relationships between them. The utilization of the randomized Inverse Variance weighted(IVW) method served as the primary analytic framework in this Mendelian Randomization (MR) study. Additionally, four alternative computational strategies, encompassing MR-Egger, were employed as auxiliary methods. A myriad of tests, including Cochran's Q Test, MR-Egger intercept test, MR-PRESSO, leave-one-out analysis, and linkage disequilibrium score were incorporated to assess the robustness of the study outcomes. Metabolite pathway analysis was also executed to identify potential metabolic pathways.
After a series of validations and corrected for False discovery rate (FDR), we found a significant association between 1,5-anhydroglucitol (OR = 2.00, 95% CI: 1.39-2.89, = 0.0002) and PH, and a significant association between pyridoxalate (OR = 0.59, 95% CI: 0.43-0.81, = 0.0009) and 1-a achidonoylglycerophosphocholine (OR = 1.78, 95% CI: 1.22-2.58, = 0.0026) had a suggested association with PH. In addition, the vitamin B6 metabolic pathway was also determined to be associated with PH.
Conclusively, we isolated 1,5-anhydroglucitol, 1-arachidonoylglycerophosphocholine, and pyridoxate as causally implicated in PH, thereby proffering substantial theoretical substantiation for the formulation of future PH prevention and screening paradigms.
最近的几项研究认为，血液中不同的代谢物可能与肺动脉高压（PH）的发病机制相关。尽管如此，PH发病机制与代谢物波动之间的相互关系仍未完全阐明，而且不同研究的结果可能存在差异。
在现有研究中，基于全基因组关联研究（GWAS）和芬兰数据库获取了来自人类受试者的486个与代谢物和PH相关的基因变异数据。采用单变量孟德尔随机化分析来评估它们之间的因果关系。在这项孟德尔随机化（MR）研究中，使用随机逆方差加权（IVW）方法作为主要分析框架。此外，还采用了包括MR-Egger在内的四种替代计算策略作为辅助方法。纳入了多种检验，包括 Cochr an's Q检验、MR-Egger截距检验、MR-PRESSO、留一法分析和连锁不平衡评分，以评估研究结果的稳健性。还进行了代谢物途径分析以识别潜在的代谢途径。
经过一系列验证并校正错误发现率（FDR）后，我们发现1,5-脱水葡萄糖醇（OR = 2.00，95%CI：1.39 - 2.89，P = 0.0002）与PH之间存在显著关联，吡哆醛酸（OR = 0.59，95%CI：0.43 - 0.81，P = 0.0009）以及1-花生四烯酰甘油磷酸胆碱（OR = 1.78，95%CI：1.22 - 2.58，P = 0.0026）与PH之间存在提示性关联。此外，还确定维生素B6代谢途径与PH相关。
最终，我们确定1,5-脱水葡萄糖醇、1-花生四烯酰甘油磷酸胆碱和吡哆醛酸与PH存在因果关系，从而为未来制定PH预防和筛查模式提供了大量理论依据。
