Inflammatory cytokines, metabolites, and pre-eclampsia: a two-sample Mendelian randomization study.

Area of Science:

• Genetics and genomics
• Metabolomics
• Reproductive health

Background:

• Pre-eclampsia (PE) is a major cause of maternal and fetal mortality.
• Inflammatory dysregulation is implicated in PE pathogenesis.
• Mendelian randomization (MR) can investigate causal relationships.

Purpose of the Study:

• To investigate the causal effects of 91 inflammatory cytokines on PE using MR.
• To identify potential mediating metabolites in PE pathogenesis.
• To uncover novel biomarkers and therapeutic targets for PE.

Main Methods:

• Two-sample MR analysis using genome-wide association study data.
• Included data on 91 inflammatory cytokines, 1400 plasma metabolites, and PE.
• Sensitivity and mediation analyses were performed to validate findings.

Main Results:

• Fibroblast growth factor 5 (FGF-5) and Matrix metalloproteinase-1 (MMP-1) were identified as novel causal risk factors for PE.
• Interleukin-10 (IL-10) and Interleukin-20 (IL-20) demonstrated protective effects against PE.
• N-acetyl-L-alanine (ALA) was identified as a significant mediator of FGF-5's effect on PE risk.

Conclusions:

• FGF-5 and MMP-1 are novel causal risk factors for PE.
• IL-10 and IL-20 are protective factors for PE.
• The identification of ALA as a mediator reveals a new metabolic-inflammatory pathway in PE pathogenesis, highlighting potential therapeutic targets.