Folate deficiency correlates with severity of primary biliary cholangitis via modulating key regulatory genes

To investigate the association between serum folate and Primary biliary cholangitis (PBC) progression through clinical, transcriptomic, and protein-level analyses.

Serum folate levels were measured in 90 patients with PBC and 90 healthy controls. RNA-sequencing (RNA-seq) was performed on three subgroups (PBC patients with normal folate, PBC patients with low folate, and controls), and six candidate genes were validated by enzyme-linked immunosorbent assay (ELISA).

Serum folate was significantly decreased in PBC patients, with further reduction in late-stage disease (p < 0.05), and negatively correlated with ALT, AST, GGT, IgG, and LSM. Combined detection of folate with DBIL and LSM achieved excellent diagnostic performance for advanced PBC (AUC = 0.974). Transcriptome analysis identified 2,363-5,648 DEGs enriched in metabolism and immune pathways. ELISA confirmed dysregulation of AHRR, MXD1, ARID3B, DECR2, and P2RY14 in PBC groups, with expression patterns linked to folate status.

Serum folate is inversely correlated with PBC severity and may serve as a potential predictive biomarker. Folate deficiency likely contributes to PBC pathogenesis by modulating key genes, including ARID3B and MXD1.