Genetic Variations in Vitamin D Metabolism Linking Epigenetic Regulation and Microbiota Interactions: From Phenotype to Genotype

Abstract

Background: Vitamin D deficiency is a global health concern affecting all age groups, despite the implementation of supplementation strategies. This study aimed to investigate the roles of genetic polymorphisms, epigenetic mechanisms, and microbiota interactions in vitamin D metabolism, as well as their potential contributions to allergies, autoimmune thyroiditis, and autism spectrum disorder.

Methods: This retrospective, descriptive study analyzed data from 60 individuals (16 males and 44 females) who underwent nutrigenetic testing between 2022 and 2024 at Epigenetic Coaching, Istanbul, Turkey. Genetic analyses focused on the cytochrome P450 family 2 subfamily R member 1 (CYP2R1) gene, group-specific component (GC) gene, and vitamin D receptor (VDR) polymorphisms. Inclusion criteria included the presence of allergic symptoms, a diagnosis of autism spectrum disorder, or a diagnosis of Hashimoto's thyroiditis, along with prior genetic testing for the selected variants. Individuals with any known genetic disorder other than the studied variants were excluded.

Results: CYP2R1, GC, and VDR polymorphisms associated with vitamin D insufficiency were found at higher frequencies in patients with autism, Hashimoto's thyroiditis, and allergic conditions. When examining the associations between genetic variants and diseases, VDR FokI, VDR ApaI, and VDR BsmI variants were more frequently observed in patients with Hashimoto's thyroiditis, while the VDR TaqI variant was more common in individuals with autism. In the allergy group, BsmI, FokI, ApaI, and TaqI variants were identified at higher frequencies.

Conclusion: Genetic variants and epigenetic modifications may disrupt vitamin D metabolism and alter gut microbiota diversity, contributing to the development of various diseases. Evaluating vitamin D deficiency together with its genetic, epigenetic, and microbiota determinants is essential for developing effective prevention and treatment strategies. These findings emphasize the necessity of personalized, nutrigenetic-based approaches to optimize vitamin D function and support overall health.