Gene Polymorphisms and Biological Effects of Vitamin D Receptor on Nonalcoholic Fatty Liver Disease Development and Progression

Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease, with increasing prevalence worldwide. The genetic and molecular background of NAFLD pathogenesis is not yet clear. The vitamin D/vitamin D receptor (VDR) axis is significantly associated with the development and progression of NAFLD. Gene polymorphisms may influence the regulation of the VDR gene, although their biological significance remains to be elucidated. VDR gene polymorphisms are associated with the presence and severity of NAFLD, as they may influence the regulation of adipose tissue activity, fibrosis, and hepatocellular carcinoma (HCC) development. Vitamin D binds to the hepatic VDR to exert its biological functions, either by activating VDR transcriptional activity to regulate gene expression associated with inflammation and fibrosis or by inducing intracellular signal transduction through VDR-mediated activation of Ca2+ channels. VDR activity has protective and detrimental effects on hepatic steatosis, a characteristic feature of NAFLD. Vitamin D-VDR signaling may control the progression of NAFLD by regulating immune responses, lipotoxicity, and fibrogenesis. Elucidation of the genetic and molecular background of VDR in the pathophysiology of NAFLD will provide new therapeutic targets for this disease through the development of VDR agonists, which already showed promising results in vivo.

Automated summary

Nonalcoholic fatty liver disease (NAFLD) is a common chronic liver disease with a rising global prevalence. The vitamin D/vitamin D receptor (VDR) axis plays a significant role in the development and progression of NAFLD. Gene polymorphisms affecting the regulation of the VDR gene are associated with the presence and severity of NAFLD, as they influence adipose tissue activity, fibrosis, and hepatocellular carcinoma (HCC) development. Vitamin D binds to the hepatic VDR, activating transcriptional activity and regulating gene expression related to inflammation and fibrosis, as well as inducing intracellular signal transduction through VDR-mediated activation of Ca2+ channels. Elucidating the genetic and molecular background of VDR in NAFLD pathophysiology can lead to the development of VDR agonists as potential therapeutic targets.