Vitamin D Receptor (VDR) Gene Polymorphisms Modify the Response to Vitamin D Supplementation: A Systematic Review and Meta-Analysis

Abstract

The vitamin D receptor (VDR), a member of the nuclear receptor superfamily of transcriptional regulators, is crucial to calcitriol signalling. VDR is regulated by genetic and environmental factors and it is hypothesised that the response to vitamin D supplementation could be modulated by genetic variants in the VDR gene. The best studied polymorphisms in the VDR gene are Apal (rs7975232), BsmI (rs1544410), Taql (rs731236) and Fokl (rs10735810). We conducted a systematic review and meta-analysis to evaluate the response to vitamin D supplementation according to the BsmI, TaqI, ApaI and FokI polymorphisms. We included studies that analysed the relationship between the response to vitamin D supplementation and the genotypic distribution of these polymorphisms. We included eight studies that enrolled 1038 subjects. The results showed no significant association with the BsmI and ApaI polymorphisms (p = 0.081 and p = 0.63) and that the variant allele (Tt+tt) of the TaqI polymorphism and the FF genotype of the FokI variant were associated with a better response to vitamin D supplementation (p = 0.02 and p < 0.001). In conclusion, the TaqI and FokI polymorphisms could play a role in the modulation of the response to vitamin D supplementation, as they are associated with a better response to supplementation.

Correlation Between Tic Disorders and Serum 25-Hydroxyvitamin D Levels in Chinese Children

“…The best studied VDR gene polymorphisms are Apal (rs7975232), Bsm I (rs1544410), Taql (rs731236), and Fokl (rs10735810). These genetic variants have been associated with a predisposition to chronic diseases such as autoimmune diseases, rheumatic arthritis, and metabolic bone diseases ( 40 – 42 ).…”

Association between Vitamin D Receptor Gene Polymorphisms and Periodontal Bacteria: A Clinical Pilot Study

“…In fact, it has been positively related to periodontitis but also to pancreatic and colic cancers [ 75 ]. Taken together, periodontal diseases may be a plausible risk factor for several diseases, including cancer, as observed at the earlier stages of disease, and ophthalmological disorders such as Pterygium, Age-related Macular Degeneration (AMD), and Diabetic Retinopathy (DR) [ 28 , 29 , 30 , 56 ]. Further studies should be encouraged for better understanding of this potential new relationship.…”

“…Research on genetic factors has focused primarily on genes modulating the immune system, such as genes encoding for the cytokines IL1A, IL1B, IL10, and IL6, considered key factors in the inflammatory process during periodontal disease [ 8 , 22 , 23 ]. Numerous studies have also been performed on vitamin D receptor (VDR) encoding gene polymorphisms BsmI, TaqI, FokI, and ApaI, opening to new considerations [ 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 ]. Once activated, the VDR protein modulates the transcription of genes that promote the functions of vitamin D, and it is established that its sequence variants are associated with dysfunctions in the metabolism of vitamin D [ 29 , 30 ].…”

“…Numerous studies have also been performed on vitamin D receptor (VDR) encoding gene polymorphisms BsmI, TaqI, FokI, and ApaI, opening to new considerations [ 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 ]. Once activated, the VDR protein modulates the transcription of genes that promote the functions of vitamin D, and it is established that its sequence variants are associated with dysfunctions in the metabolism of vitamin D [ 29 , 30 ]. These SNPs have been considered a key factor in the reabsorption of alveolar bone and increased bone cell turnover resulting in an increased risk of reduced bone mass density (BMD) and osteoporosis [ 32 ].…”

The Multiple Effects of Vitamin D against Chronic Diseases: From Reduction of Lipid Peroxidation to Updated Evidence from Clinical Studies

“…Bsm I (rs1544410) is located in intron 8 of the gene and consists in A > G nucleotide substitution, influencing transcript stability. The A nucleotide corresponds to allele B, and the G nucleotide corresponds to allele b. Fok I is a T > C nucleotide substitution on the VDR gene codon start (ATG → ACG) [ 82 , 83 , 84 ]. This shortened protein gains greater transcription activity due to the minor steric bulk of the molecule at the binding site of the transcription factor IIB [ 85 ].…”