Genetic regulation of the expression of two fibrinogen gamma chain splice variants by fibrin degeneration products and inflammatory cytokines

Fibrinogen and its γ’ isoform are key predictors of cardiovascular disease, yet the mechanisms regulating their production are not fully defined. This work identifies IFN‑γ as a novel suppressor of total fibrinogen via STAT1 and its interference with IL‑6 signaling. IL‑6, IFN‑γ, and TNF‑α are shown to differentially modulate γ’ versus total fibrinogen. We also demonstrate that D‑dimer enters hepatocyte‑derived cells and decreases γ’ fibrinogen synthesis. Finally, we characterize a γR275C fibrinogen mutation that produces a hemorrhagic phenotype, revealing its pathogenic potential.