The Role of Polymorphisms in Vitamin D-Related Genes in Response to Vitamin D Supplementation.

ABSTRACT: BACKGROUND:Vitamin D deficiency represents a major healthcare problem. Vitamin D status is influenced by genetic and environmental determinants. Several observational studies have evaluated the association of single-nucleotide polymorphisms (SNPs) in vitamin D-related genes and vitamin D levels. Nevertheless, little is known about the role of these SNPs in the response to vitamin D supplementation. We conducted an interventional study to define the association between SNPs in vitamin D-related genes and the response to vitamin D supplementation in 100 self-reported healthy women of Arab ancestry for the majority. METHODS:A total of 100 healthy female subjects received a weekly oral dose of 50,000 IU vitamin D for 12 weeks. Serum vitamin D concentration and metabolic profiles were measured at baseline and 12 weeks post-vitamin D supplementation. The genotypes of 37 SNPs selected from previously reported vitamin D-related genes have been assessed by Fluidigm genotyping assay. RESULTS:Rs731236 (VDR gene) and rs7116978 (CYP2R1 gene) showed a significant association with vitamin D status. The rs731236 GG genotype and the rs7116978 CC genotype were associated with a "vitamin D sufficiency" state. Rs731236 GG and rs7116978 CC genotypes showed a higher response to vitamin D supplementation. Transcription factor binding site prediction analysis showed altered binding sites for transcription factors according to the different rs7116978 alleles. Interestingly, the 37 SNPs previously established to play a role in vitamin D-related pathways explained very little of the response to vitamin D supplementation in our cohort, suggesting the existence of alternative loci whose number and effect size need to be investigated in future studies. CONCLUSION:In this paper, we present novel data on vitamin D-related SNPs and response to vitamin D supplementation demonstrating the feasibility of applying functional genomic approaches in interventional studies to assess individual-level responses to vitamin D supplementation.

SUBMITTER: Tomei S 

PROVIDER: S-EPMC7551134 | biostudies-literature | 2020 Aug

REPOSITORIES: biostudies-literature