National Center for Birth Defects Monitoring of China, West China Second University Hospital, Sichuan University, Chengdu, Sichuan, China.
Key Laboratory of Birth Defects and Related Diseases of Women and Children (Sichuan University), Ministry of Education, Chengdu, Sichuan, China.
BMC Pregnancy Childbirth. 2024 Aug 20;24(1):547. doi: 10.1186/s12884-024-06738-y.
The congenital ventricular outflow tract malformations (CVOTMs) is a major congenital heart diseases (CHDs) subtype, and its pathogenesis is complex and unclear. Lipid metabolic plays a crucial role in embryonic cardiovascular development. However, due to the limited types of detectable metabolites in previous studies, findings on lipid metabolic and CHDs are still inconsistent, and the possible mechanism of CHDs remains unclear.
The nest case-control study obtained subjects from the multicenter China Teratology Birth Cohort (CTBC), and maternal serum from the pregnant women enrolled during the first trimester was utilized. The subjects were divided into a discovery set and a validation set. The metabolomics of CVOTMs and normal fetuses were analyzed by targeted lipid metabolomics. Differential comparison, random forest and lasso regression were used to screen metabolic biomarkers.
The lipid metabolites were distributed differentially between the cases and controls. Setting the selection criteria of P value < 0.05, and fold change (FC) > 1.2 or < 0.833, we screened 70 differential metabolites. Within the prediction model by random forest and lasso regression, DG (14:0_18:0), DG (20:0_18:0), Cer (d18:2/20:0), Cer (d18:1/20:0) and LPC (0:0/18:1) showed good prediction effects in discovery and validation sets. Differential metabolites were mainly concentrated in glycerolipid and glycerophospholipids metabolism, insulin resistance and lipid & atherosclerosis pathways, which may be related to the occurrence and development of CVOTMs.
Findings in this study provide a new metabolite data source for the research on CHDs. The differential metabolites and involved metabolic pathways may suggest new ideas for further mechanistic exploration of CHDs, and the selected biomarkers may provide some new clues for detection of COVTMs.
先天性心室流出道畸形（CVOTMs）是一种主要的先天性心脏病（CHDs）亚型，其发病机制复杂且尚不清楚。脂质代谢在胚胎心血管发育中起着至关重要的作用。然而，由于先前研究中可检测代谢物的类型有限，脂质代谢与 CHDs 的研究结果仍然不一致，CHDs 的可能机制仍不清楚。
巢式病例对照研究从多中心中国出生队列研究（CTBC）中获取受试者，利用纳入孕妇在孕早期的血清。将受试者分为发现集和验证集。通过靶向脂质代谢组学分析 CVOTMs 和正常胎儿的代谢组学。使用差异比较、随机森林和套索回归筛选代谢生物标志物。
病例组和对照组之间的脂质代谢物分布存在差异。设定 P 值 < 0.05，倍数变化（FC）> 1.2 或 < 0.833 的选择标准，筛选出 70 个差异代谢物。在随机森林和套索回归的预测模型中，DG（14:0_18:0）、DG（20:0_18:0）、Cer（d18:2/20:0）、Cer（d18:1/20:0）和 LPC（0:0/18:1）在发现集和验证集中均表现出良好的预测效果。差异代谢物主要集中在甘油磷脂代谢、胰岛素抵抗和脂质与动脉粥样硬化途径，这可能与 CVOTMs 的发生和发展有关。
本研究提供了 CHDs 研究的新代谢物数据源。差异代谢物及其涉及的代谢途径可能为进一步探索 CHDs 的发病机制提供新的思路，所选生物标志物可能为检测 CVOTMs 提供一些新的线索。
