KRT23 as a Potential Target for Metabolic Dysfunction-Associated Fatty Liver Disease (MAFLD): Evidence From Bioinformatics Analysis, Human Gene Polymorphism and Animal Experiments.

BACKGROUND

Metabolic dysfunction-associated fatty liver disease (MAFLD) is highly prevalent in Xinjiang, with genetic factors influencing its pathogenesis. Keratin 23 (KRT23), a liver-enriched protein linked to metabolic regulation, remains understudied in MAFLD genetics.

OBJECTIVE

To investigate associations between KRT23 gene polymorphisms, expression, and MAFLD in Xinjiang.

METHODS

This study enrolled 1,795 MAFLD patients diagnosed via ultrasonography and metabolic criteria. KRT23 polymorphisms (rs72826004, rs2269859) were analyzed. GEO database screening identified MAFLD-related genes. KRT23 expression was assessed in human serum/liver tissues (ELISA, Western blot, qRT‒PCR, IHC) and murine models (high-fat diet-induced MAFLD and db/db mice).

RESULTS

Enrichment analysis identified 10 key MAFLD-associated genes, including KRT23. The rs72826004 TT genotype increased MAFLD risk (OR: 2.156, P=0.007), while rs2269859 TT conferred protection (OR: 0.306, P=0.002). MAFLD patients exhibited elevated KRT23 protein/mRNA levels in serum and liver versus controls. Murine models confirmed higher KRT23 expression in MAFLD and db/db mice compared to wild-type.

CONCLUSION

KRT23 gene polymorphism was associated with the occurrence of MAFLD. The rs72826004 loci TT genotype may be a risk factor for MAFLD, whereas the rs2269859 loci TT genotype may be a protective factor against MAFLD. Higher KRT23 expression (protein and mRNA) is related to MAFLD. KRT23 is a potential target for the treatment of MAFLD.