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

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.

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