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 x 10(-8)), high body mass index (p = 2.13 x 10(-2)), low total-cholesterol (p = 1.46 x 10(-4)), low serum vitamin D level (p = 7.34 x 10(-3)), and VDR rs1544410 genotype CC (p = 9.15 x 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. (C) 2019 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.