Association of vitamin D levels and vitamin D-related gene polymorphisms with liver fibrosis in patients with biopsy-proven nonalcoholic fatty liver disease

Dig Liver Dis. 2019 Jul;51(7):1036-1042. doi: 10.1016/j.dld.2018.12.022. Epub 2019 Jan 9.


Background: Vitamin D has promising anti-proliferative and anti-fibrotic properties, but its clinical utility in nonalcoholic fatty liver disease (NAFLD) is unclear.

Aims: This study aimed to clarify the association between vitamin D levels, single nucleotide polymorphisms (SNPs) in vitamin D-related genes, and the histopathological severity of disease in patients with biopsy-proven NAFLD.

Methods: SNPs in CYP2R1, DHCR7, vitamin D binding protein (GC), CYP27B1, and vitamin D receptor (VDR) were determined for 229 consecutive patients with biopsy-proven NAFLD.

Results: In this study, vitamin D deficiency defined as 25-hydroxyvitamin-D3 levels of ≤20 ng/mL was found in 151 patients (65.9%). Multivariate analysis revealed that cold season, advanced fibrosis, and CYP2R1 rs1993116 genotype non-AA were independent factors significantly associated with vitamin D deficiency. Old age (p = 5.05 × 10-8), high body mass index (p = 2.13 × 10-2), low total-cholesterol (p = 1.46 × 10-4), low serum vitamin D level (p = 7.34 × 10-3), and VDR rs1544410 genotype CC (p = 9.15 × 10-3) were independent factors associated with advanced liver fibrosis.

Conclusion: Serum 25-hydroxyvitamin-D3 levels and the VDR gene SNP were significantly and independently associated with the severity of liver fibrosis in patients with biopsy-proven NAFLD.

Keywords: Histopathological liver severity; NAFLD; Vitamin D receptor gene.

Publication types

  • Multicenter Study

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Body Mass Index
  • Calcifediol / blood*
  • Cholestanetriol 26-Monooxygenase / genetics*
  • Cytochrome P450 Family 2 / genetics*
  • Female
  • Genotype
  • Humans
  • Japan
  • Liver Cirrhosis / blood
  • Liver Cirrhosis / genetics*
  • Logistic Models
  • Male
  • Middle Aged
  • Multivariate Analysis
  • Non-alcoholic Fatty Liver Disease / complications*
  • Non-alcoholic Fatty Liver Disease / pathology
  • Polymorphism, Single Nucleotide*
  • Receptors, Calcitriol / genetics*
  • Young Adult


  • Receptors, Calcitriol
  • VDR protein, human
  • Cytochrome P450 Family 2
  • CYP2R1 protein, human
  • Cholestanetriol 26-Monooxygenase
  • Calcifediol