Dysregulation and gene polymorphisms of Vitamin D receptor: its implications in lipid metabolic disorders

The intricate relationship between vitamin D and metabolic homeostasis has garnered substantial attention recently. The presence of the vitamin D receptor (VDR) in many tissues provides evidence of its broad physiological roles, in addition to its impact on calcium and phosphorus metabolism. VDR gene is expressed in various tissues such as skin, adipose tissue, testis, thyroid, esophagus, etc. Decreased VDR expression is associated with numerous complications such as muscle weakness, poor cancer prognosis, coronary restenosis, cognitive disability, susceptibility to autoimmune diseases, diabetes, and others. Conversely, overexpression of VDR can result in pathological conditions such as hypercalcemia, soft tissue calcification, kidney damage, cardiovascular complications, skeletal muscle hypertrophy, and cancer cell invasion and metastasis, leading to cancer cell proliferation. Therefore, it is crucial to maintain proper and balanced VDR expression, as both its downregulation and upregulation can lead to significant consequences. The genetic variants in the VDR gene, particularly ApaI (rs7975232), BsmI (rs1544410), FokI (rs2228570) and TaqI (rs731236), play a significant role in regulating lipid homeostasis. VDR gene polymorphisms are associated with several disease conditions such as inflammatory bowel disease, multiple sclerosis, pulmonary tuberculosis, asthma and gestational diabetes mellitus, in addition to lipid metabolic disorders. This review explores the emerging body of literature that sheds light on the dysregulation of VDR expression, VDR gene polymorphisms, and their implications in metabolic disorders, with a particular focus on lipid metabolism. With an emphasis on unraveling the molecular intricacies of this phenomenon, this review explores the multifaceted role of the VDR in key metabolic pathways and its potential involvement in lipid-associated conditions such as obesity, dyslipidemia, fatty liver disease, and atherosclerosis.