Association of MCP-4, NRTN, and PD-L1 with the risk of hepatic fibrosis: A Mendelian randomization study.

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.