Multi-dimensional insights into the association between PFOA exposure and NAFLD: An integrative analysis of epidemiology, transcriptomics, and molecular docking

Perfluorooctanoic acid (PFOA), a persistent organic pollutant from the PFAS family, is widely detected in the environment and human blood, raising significant concerns about its long-term health effects. This study explores the potential association between serum PFOA exposure and non-alcoholic fatty liver disease (NAFLD) by integrating data from the NHANES 2003-2012 cohort, global disease burden data (GBD 2021), and toxicogenomic analyses. Weighted logistic regression revealed that individuals in the highest tertile of PFOA exposure had a significantly increased risk of NAFLD (adjusted OR = 1.45, 95 % CI: 1.01-2.07). Restricted cubic spline analysis further supported a nonlinear dose-response relationship. Transcriptomic analysis identified five hub genes (IL6, IL1B, FOS, MYC, CDKN1A) potentially involved in lipid metabolism, inflammation, and cell cycle regulation. Molecular docking suggested high binding energy between PFOA and the encoded proteins, indicating possible interference with key hepatic functions. Together, these findings offer preliminary insights into potential mechanisms by which environmentally relevant levels of PFOA might be involved in NAFLD development. This integrative approach serves as a hypothesis-generating framework for future studies on biomarker discovery, risk assessment, and environmental health policy.