Association Between Iron Overload and Metabolic Dysfunction-Associated Steatotic Liver Disease:Based on NHANES and Transcriptomic Data
LI Qian
SONG Jieyun
YU Ning
XU Lisha
SONG Yi
WANG Liangjun
Abstract：Objective By integrating epidemiological and transcriptomic data,this study investigates the relationship between iron overload and metabolic dysfunction-associated steatotic liver disease(MASLD),explores the underlying molecular mechanisms linking iron overload to the onset and progression of MASLD,and provides a scientific basis for clinical targeted diagnosis,treatment,or interventions.Methods Utilizing data from the NHANES 2017-2020,multivariable Logistic regression analysis was employed to assess the relationship between iron overload and the risk of MASLD.Multivariable linear regression was used to evaluate the association between iron overload and four types of liver enzymes.Subsequently,GEO dataset(GSE126848)and FerrDb V2 data were analyzed.Weighted Gene Co-expression Network Analysis(WGCNA)was applied to identify modules associated with MASLD.Protein-Protein Interaction(PPI)network was constructed to identify key genes.Results This study ultimately included 2010 participants:769 in the MASLD group and 1241 in the non-MASLD group.The results of multivariate Logistic regression analysis showed that after adjusting for age,gender,ethnicity,smoking status,and BMI,iron overload was associated with the risk of MASLD(OR=1.315,95％CI:1.041-1.661,P=0.022).Under the same adjusted variables,multiple linear regression analysis was used and it was found that iron overload was correlated with elevated levels of ALT,AST and GGT(P＜0.001).A total of 2,077 MASLD-related genes were obtained from the GSE126848 dataset of the GEO database,and 484 genes related to iron overload were finally determined from the FerrDb database.After analysis by the WGCNA and PPI networks,five potential core genes simultaneously related to iron overload and MASLD were finally obtained:TGFB1,HMOX1,HSPA5,CDKN1A and CTSB.Conclusion This study discovered the correlation between iron overload and MASLD as well as liver enzyme levels,analyzed and identified potential key genes related to iron overload and MASLD,and explored the potential functional mechanisms between iron metabolism and MASLD at the molecular level.
Keywords：iron overloadmetabolic dysfunction-associated steatotic liver diseaseweighted gene co-expression network analysis
Publication Date：2025-08-30
Online Publishing Date：2025-10-17(First online date of this platform, not the publication date of the document)
Pages：6( 96-101 )