Related Experiment Video
Updated: Jul 8, 2025
Determination of Fatty Acid Oxidation and Lipogenesis in Mouse Primary Hepatocytes
Published on: August 27, 2015
Iron status and non-alcoholic fatty liver disease: A Mendelian randomization study
Kexin Sun1, Jie V Zhao2, Edmund Anthony Severn Nelson3
1Department of Paediatrics, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong SAR, PR China.
Objectives:
The aim of this study was to assess the association of genetically determined iron status with the risk for non-alcoholic fatty liver disease (NAFLD) using two-sample Mendelian randomization (MR) analysis.
Methods:
We applied single nucleotide polymorphisms (SNPs) associated at genome-wide significance with iron status proxied by serum iron, ferritin, transferrin, and transferrin saturation from the Genetics of Iron status Consortium (N = 48 793), in a genome-wide association study of 1664 NAFLD cases and 400 055 controls from the United Kingdom Biobank. A SNP associated with multiple markers of iron status was only applied to one marker with the strongest association in the main analysis. Their effects on NAFLD were calculated using inverse variance weighting after excluding SNPs associated with alkaline phosphatase and lipid metabolism.
Results:
The risk for NAFLD is negatively associated with genetically predicted serum transferrin level with a 20% reduction in NAFLD risk per SD (0.65g/L) increase in transferrin (95% confidence interval [CI], 0.66-0.97), and trending positive association with transferrin saturation (odds ratio [OR], 1.50; 95% CI, 0.96-2.35) but it was not associated with serum iron (OR, 0.90; 95% CI, 0.63-1.29) and ferritin (OR, 1.33; 95% CI, 0.54-3.30).
Conclusions:
MR analysis provided evidence that genetically predicted higher serum transferrin, indicating lower iron status, may be protective against NAFLD, whereas higher transferrin saturation, indicating higher iron status, might increase the risk for NAFLD and its pathogenesis.
