Division of Gastroenterology, Department of Internal Medicine, Medical School, University of Patras, University Hospital of Patras, 26504 Patras, Greece.
Division of Hematology, Department of Internal Medicine, Medical School, University of Patras, 26504 Patras, Greece.
Int J Mol Sci. 2023 Jul 13;24(14):11404. doi: 10.3390/ijms241411404.
Single nucleotide polymorphisms (SNPs) in the vitamin D receptor (VDR) gene have been associated with chronic liver disease. We investigated the role of VDR SNPs on VDR protein levels and function in patients with chronic liver disease. VDR expression levels were determined in peripheral T lymphocytes (CD3+VDR+), monocytes (CD14+VDR+), and plasma from patients ( = 66) and healthy controls ( = 38). Genotyping of SNPs and the determination of expression of VDR/vitamin D-related genes were performed by using qPCR. The effect of FokI SNP on vitamin D-binding to VDR was investigated by molecular dynamics simulations. CD14+VDR+ cells were correlated with the MELD score. The ApaI SNP was associated with decreased CD3+VDR+ levels in cirrhotic patients and with higher liver stiffness in HCV patients. The BsmI and TaqI SNPs were associated with increased VDR plasma concentrations in cirrhotic patients and decreased CD14+VDR+ levels in HCV patients. The FokI SNP was associated with increased CD3+VDR+ levels in cirrhotic patients and controls. VDR polymorphisms were significantly related to the expression of genes critical for normal hepatocyte function and immune homeostasis. VDR expression levels were related to the clinical severity of liver disease. VDR SNPs may be related to the progression of chronic liver disease by affecting VDR expression levels.
单核苷酸多态性（SNPs）在维生素 D 受体（VDR）基因中与慢性肝病有关。我们研究了 VDR SNPs 对慢性肝病患者 VDR 蛋白水平和功能的作用。在来自患者（n=66）和健康对照者（n=38）的外周 T 淋巴细胞（CD3+VDR+）、单核细胞（CD14+VDR+）和血浆中测定了 VDR 表达水平。通过 qPCR 进行了 SNPs 的基因分型和 VDR/维生素 D 相关基因的表达测定。通过分子动力学模拟研究了 FokI SNP 对维生素 D 与 VDR 结合的影响。CD14+VDR+细胞与 MELD 评分相关。ApaI SNP 与肝硬化患者的 CD3+VDR+水平降低以及 HCV 患者的肝硬度增加相关。BsmI 和 TaqI SNP 与肝硬化患者 VDR 血浆浓度升高和 HCV 患者 CD14+VDR+水平降低相关。FokI SNP 与肝硬化患者和对照者的 CD3+VDR+水平升高相关。VDR 多态性与正常肝细胞功能和免疫平衡的关键基因表达显著相关。VDR 表达水平与肝病的临床严重程度相关。VDR SNPs 可能通过影响 VDR 表达水平而与慢性肝病的进展有关。
