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Association of MCP-4, NRTN, and PD-L1 with the risk of hepatic fibrosis: A Mendelian randomization study
Liqun Li1, Jing Yan2, Qian Liu1
1First Affiliated Hospital of Guangxi University of Chinese Medicine, Nanning City, China.
Abstract:
Previous studies have confirmed the affiliation between specific inflammatory cytokines and Hepatic fibrosis (HF); however, contradictions remain in the causality. The study implemented a bidirectional two-sample Mendelian randomization (MR) analysis with published statistics derived from Genome-wide Association Studies (GWAS) to investigate casualties between inflammatory cytokines and HF. Additionally, MR analysis was also introduced to consider if 1400 blood metabolites act as the key mediators in this process. Single nucleotide polymorphisms (SNPs) with strong correlations to inflammatory factors were selected for multiple MR analyses in this study. The inverse variance weighted method (IVW) was chosen as the principal analysis, and the others as the supportive. Besides, sensitivity tests were involved to identify potential heterogeneity and pleiotropic level. IVW methods revealed that a relatively high level of prediction-based monocyte chemoattractant protein-4 (MCP-4) (95% CI: 1.014-3.336, P = .045), along with neurturin (NRTN) (95% CI: 1.204-4.004, P = .010), may increase the risk of HF; while programmed cell death 1 ligand 1 (PD-L1) (95% CI: 0.223-0.928, P = .030), showed a protective effect on HF. No significant statistical differences were detected on any other inflammatory cytokines, nor did the impact of HF genetic predisposition on the 91 circulating inflammatory cytokines-related characteristics.
Insights
This study investigated the causal link between inflammatory cytokines and hepatic fibrosis (HF). High levels of monocyte chemoattractant protein-4 (MCP-4) and neurturin (NRTN) may increase HF risk, while programmed cell death 1 ligand 1 (PD-L1) may offer protection.
Area of Science:
- Genetics and Molecular Biology
- Immunology
- Hepatology
Background:
- Inflammatory cytokines are linked to hepatic fibrosis (HF), but causality is debated.
- Mendelian randomization (MR) offers a robust method to explore genetic causality.
Purpose of the Study:
- To investigate the causal relationship between inflammatory cytokines and HF using a bidirectional two-sample MR analysis.
- To explore the potential mediating role of 1400 blood metabolites in this relationship.
Main Methods:
- Utilized Genome-wide Association Studies (GWAS) data for MR analysis.
- Employed the inverse variance weighted (IVW) method as the primary analysis, supported by sensitivity tests.
- Selected single nucleotide polymorphisms (SNPs) strongly correlated with inflammatory factors.
Main Results:
- Elevated monocyte chemoattractant protein-4 (MCP-4) and neurturin (NRTN) were associated with increased HF risk.
- Programmed cell death 1 ligand 1 (PD-L1) demonstrated a protective effect against HF.
- No significant causal links were found for other inflammatory cytokines or HF's impact on them.
Conclusions:
- Specific inflammatory cytokines, MCP-4 and NRTN, may causally contribute to hepatic fibrosis development.
- PD-L1 may play a protective role in hepatic fibrosis.
- Further research is warranted to elucidate the complex interplay between inflammation, metabolites, and HF.
