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Biomarkers for congenital ventricular outflow tract malformations based on maternal serum lipid metabolomics analysis
Xuelian Yuan1,2, Hong Kang1,2, Yuqin Qin3
1National Center for Birth Defects Monitoring of China, West China Second University Hospital, Sichuan University, Chengdu, Sichuan, China.
Insights
This study identifies specific lipid metabolites linked to congenital ventricular outflow tract malformations (CVOTMs), a type of congenital heart disease (CHD). These findings offer new insights into CHD mechanisms and potential biomarkers for detection.
Area of Science:
- Biochemistry
- Developmental Biology
- Cardiovascular Science
Background:
- Congenital ventricular outflow tract malformations (CVOTMs) are a significant subtype of congenital heart diseases (CHDs) with complex and unclear pathogenesis.
- Lipid metabolism is crucial for embryonic cardiovascular development, but previous findings on its role in CHDs are inconsistent due to limited metabolite analysis.
Purpose of the Study:
- To investigate the role of lipid metabolism in the pathogenesis of CVOTMs.
- To identify potential metabolic biomarkers for the early detection of CVOTMs.
Main Methods:
- A case-control study using maternal serum from the China Teratology Birth Cohort (CTBC).
- Targeted lipid metabolomics analysis was performed on samples from fetuses with CVOTMs and normal controls.
- Differential comparison, random forest, and lasso regression were employed to screen for metabolic biomarkers.
Main Results:
- Significant differences in lipid metabolites were observed between CVOTMs cases and controls.
- Seventy differential metabolites were identified, with 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) showing strong predictive effects.
- Enriched pathways included glycerolipid and glycerophospholipids metabolism, insulin resistance, and lipid & atherosclerosis.
Conclusions:
- This study provides novel metabolite data for CHD research.
- Identified differential metabolites and pathways may offer new avenues for exploring CVOTM mechanisms.
- Selected biomarkers could aid in the detection of CVOTMs.
Background:
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.
Methods:
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.
Results:
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.
Conclusion:
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.
