Document Type
Article
Publication Date
6-19-2024
Original Citation
Koch R,
Stanton J,
McClatchy S,
Churchill G,
Craig S,
Williams D,
Johns M,
Chase K,
Thiesfeldt D,
Flynt J,
Pazdro R.
Discovery of genomic loci for liver health and steatosis reveals overlap with glutathione redox genetics. Redox Biol. 2024;75:103248.
Keywords
JMG
JAX Source
Redox Biol. 2024;75:103248.
ISSN
2213-2317
PMID
38917671
DOI
https://doi.org/10.1016/j.redox.2024.103248
Grant
This work was supported by the National Institutes of Health - National Institute of General Medical Sciences R01 GM121551.
Abstract
Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver condition in the United States, encompassing a wide spectrum of liver pathologies including steatosis, steatohepatitis, fibrosis, and cirrhosis. Despite its high prevalence, there are no medications currently approved by the Food and Drug Administration for the treatment of NAFLD. Recent work has suggested that NAFLD has a strong genetic component and identifying causative genes will improve our understanding of the molecular mechanisms contributing to NAFLD and yield targets for future therapeutic investigations. Oxidative stress is known to play an important role in NAFLD pathogenesis, yet the underlying mechanisms accounting for disturbances in redox status are not entirely understood. To better understand the relationship between the glutathione redox system and signs of NAFLD in a genetically-diverse population, we measured liver weight, serum biomarkers aspartate aminotransferase (AST) and alanine aminotransferase (ALT), and graded liver pathology in a large cohort of Diversity Outbred mice. We compared hepatic endpoints to those of the glutathione redox system previously measured in the livers and kidneys of the same mice, and we screened for statistical and genetic associations using the R/qtl2 software. We discovered several novel genetic loci associated with markers of liver health, including loci that were associated with both liver steatosis and glutathione redox status. Candidate genes within each locus point to possible new mechanisms underlying the complex relationship between NAFLD and the glutathione redox system, which could have translational implications for future studies targeting NAFLD pathology.
Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 International License.