Correlation of polymorphous variants (ApaI, TagI, BsmI) of the VDR receptor gene with the vitamin D level and liver fibrosis in children with autoimmune hepatitis

Abstract

The aim. To study the correlation of the frequency distribution of alleles, genotypes and their combinations for the allelic variants of ApaI, TagI, BsmI of the Vitamin D receptor gene (VDR) with the vitamin D levels and the stage of fibrosis in children with autoimmune hepatitis.Materials and methods. 51 children with autoimmune hepatitis were examined between 2016 and 2018. In all children, the diagnosis was confirmed in accordance with the International Guidelines for the study of liver diseases (European Association for the Study of Liver (EASL) Clinical Practice Guidelines: Autoimmune Hepatitis, 2015). In the examined children, the elastography of the liver parenchyma was performed by the shear wave method. Needle biopsy of the liver with histological examination of the specimens was performed in 42 children. The disease activity was determined using the histological activity index (HAI) by Knodell based on the results of a morphological study of the liver biopsy and biochemical parameters. The stage of the disease was evaluated by the histological index of fibrosis using the METAVIR scoring system and semi-quantitatively using the share wave elastography of liver parenchyma. A level of 25(OH)D was determined in the blood serum. The determination of the ApaI, TagI, BsmI polymorphic loci of vitamin D receptor (VDR) was carried out using the molecular-genetic method. The association of polymorphic variants of the VDR gene with the level of vitamin D and the stage of liver fibrosis in children with autoimmune hepatitis has been evaluated.Results. 72.0 % of the examined children had advanced severe liver fibrosis (F3-4 by the METAVIR score), among them 34.0 % of children had signs of liver cirrhosis. Children with advanced severe fibrosis (F3–4 by the METAVIR score) had the CC genotype of the polymorphic version of the TagI of the VDR gene significantly more often (χ2 = 3.953; P < 0.05), and the genotype AA/CC/AA according to the investigated allelic variants of the VDR gene (χ2 = 3.953; P < 0.05). In 72.5 % of the examined children, there was a deficiency of vitamin D. In children with severe fibrosis (F3–4 by the METAVIR score) vitamin D deficiency was significantly more frequent as compared to children with less severe fibrosis (F1–2 by the METAVIR score) (χ2 = 5,207; P = 0.023). The genotype GA of the BsmI polymorphic variant was associated with a decrease in serum vitamin D levels (P < 0.05). At the AC/TC/GA combination of the ApaI, TagI and BsmI allelic variants of the VDR gene, vitamin D deficiency was registered significantly more frequently (P < 0.05).Conclusions. The level of vitamin D in children with autoimmune hepatitis was dependent on the stage of fibrosis. Children with severe fibrosis had a genetically determined vitamin D deficiency significantly more often. Vitamin D deficiency was associated with the CC genotype presence of the TagI polymorphic variant of the VDR gene in patients as well as the GA genotype of the BsmI polymorphic variant and the AC/TC/GA genotype of the three allelic variants of the gene studied.