Genetic variations in Vitamin D metabolism genes and the microbiome, in the presence of adverse environmental changes, increase immune dysregulation

Abstract

Vitamin D metabolism in individuals is affected not only by their exposure to the sun or dietary intake of vitamin D, their liver and kidney function and other tissue production, but also by genetic variations in genes associated with vitamin D metabolism. These genes include not only the vitamin D receptor (VDR) genes, but also Group–Specific Component (GC), 7-dehydrocholesterol reductase (DHCR7), cytochrome P450 2R1(CYP2R1), cytochrome P450, family 24, subfamily A, polypeptide 1 (CYP24A1), and cytochrome p450 27B1 (CYP27B1). Particular single nucleotide polymorphisms (SNPs) from a number of these genes are being associated with lower or higher circulating vitamin D concentrations. Vitamin D metabolism is also affected by interactions with the individual’s microbiome. Other environmental changes in addition to vitamin D intake, particularly those associated with variations in nutrient intake and exposure to pathogens, can impact on these gene variations associated with vitamin D metabolism. Certain combinations of these, in addition to a lowering of circulating vitamin D, influence immune and metabolic pathways and contribute to immune dysregulation. The current enhancement and interplay of these permutations augurs the rise of chronic conditions in the Western world. To ameliorate this, vitamin D supplementation needs to be tailored to an individual’s genotype in the context of their environment.(CYP27B1). Particular single nucleotide polymorphisms (SNPs) from a number of these genes are being associated with lower or higher circulating vitamin D concentrations. Vitamin D metabolism is also affected by interactions with the individual’s microbiome. Other environmental changes in addition to vitamin D intake, particularly those associated with variations in nutrient intake and exposure to pathogens, can impact on these gene variations associated with vitamin D metabolism. Certain combinations of these, in addition to a lowering of circulating vitamin D, influence immune and metabolic pathways and contribute to immune dysregulation. The current enhancement and interplay of these permutations augurs the rise of chronic conditions in the Western world. To ameliorate this, vitamin D supplementation needs to be tailored to an individual’s genotype in the context of their environment. Keywords: Genetic Variations; Vitamin D; Immune Dysregulation