Genetic and Epigenetic Determinants of Vitamin D Metabolism: Nutrigenomic Insights for Precision Nutrition

Abstract

Vitamin D plays a pivotal role in immune regulation, metabolic balance, skeletal health, and gene expression. Growing evidence indicates that genetic and epigenetic factors contribute to interindividual differences in vitamin D status and physiological responses. This review summarizes current findings on the nutrigenomic determinants of vitamin D metabolism, with emphasis on genetic polymorphisms in vitamin D receptor (VDR), GC, CYP2R1, CYP27B1, and CYP24A1, as well as epigenetic mechanisms that modulate vitamin D related gene expression. Peer-reviewed original studies and review articles published between 2010 and 2025 were examined to highlight associations between genetic variation in the vitamin D pathway and susceptibility to cancer, autoimmune disorders, metabolic diseases, cardiovascular conditions, and neurodegenerative outcomes. Advances in omics technologies and epigenetic biomarker research have improved understanding the molecular pathways through which vitamin D acts across multiple body systems. Evidence from gene–environment interactions and genotype-specific supplementation responses highlights the conceptual relevance of precision nutrition, while underscoring substantial gaps in clinical validation. Collectively, current research suggests that genetic information may inform future personalized vitamin D strategies, although translation into clinical practice remains limited by inconsistent evidence and methodological heterogeneity.