Vitamin D receptor gene ApaI and FokI polymorphisms and its association with inflammation and oxidative stress in vitamin D sufficient Caucasian Spanish children

Abstract

Background: Vitamin D has gone from being just one vitamin to being an important prohormone with multiple effects on different tissue types. The mechanism of action of the active form or calcitriol is mediated by the intracellular vitamin D receptor (VDR). The interaction of the VDR with calcitriol modulates the expression of target genes involved in cell proliferation and cytokine production. Several studies have explored the effects of vitamin D deficiency in inflammatory disorders. Furthermore, some mutations in the VDR can affect its functionality. The focus of this study was to explore associations between VDR single nucleotide polymorphisms (SNPs) and markers of inflammation and oxidative stress in vitamin D sufficient children.Methods: This is a cross-sectional study of a Caucasian Spanish population including 155 healthy children (87 males, 68 females) aged 10 to 14 years. FokI, ApaI and TaqI SNPs of the VDR gene were genotyped.Routine biochemistry, serum levels of interleukin-6, tumor necrosis factor-α, interferon-γ, 8-isoprostaglandin F2α and nitrates were determined. Results:The homozygous major allele AA in the FokI SNP was associated with increased levels of highdensity lipoprotein cholesterol in a recessive inheritance mode (P=0.025). The minor allele A of ApaI was significantly associated with decreased serum tumor necrosis factor-α and 8-isoprostaglandin F2α in an additive mode (P=0.016 and P=0.020 respectively). No significant associations were observed between the TaqI SNP and any of the parameters evaluated. Haplotype analysis confirmed the significance of the relationships between ApaI and FokI SNPs and parameters associated with inflammation and oxidative stress.Conclusions: Genetic variations of VDR are associated with subtle changes in metabolic, inflammatory and oxidative stress markers. These results may provide a better understanding of the relationships between vitamin D and these clinical parameters.

Vitamin D Determinants, Status, and Antioxidant/Anti-inflammatory-Related Effects in Cardiovascular Risk and Disease: Not the Last Word in the Controversy

“…Interestingly, recent data suggested that genetic variations of VDR are associated with changes in metabolic, inflammatory, and oxidative stress parameters in children, providing evidence of how specific VDR polymorphisms may play a role in general susceptibility or protection to cardiometabolic risk and diseases through these clinical biomarkers [ 101 ].…”

Vitamin D status, vitamin D receptor gene polymorphism, and haplotype in patients with cutaneous leishmaniasis: Correlation with susceptibility and parasite load index

“…However, the frequency of the “B-a-T-F” haplotype of vitamin D receptor gene polymorphisms was significantly greater in control patients compared to CL patients and could be protective against CL, as the odds of having the haplotype were lower among CL patients compared to controls, suggesting that this haplotype may have the potential to protect against cutaneous leishmaniasis susceptibility These results revealed that the presence of the “A” allele in ApaI SNP of VDR and “B-A-T-F” haplotype increases the susceptibility to CL, while “a” allele and “B-a-T-F ” haplotype may have potential protection against CL and these are novel findings which have not been reported before. A previous study found that the A allele in the ApaI SNP was related to lower serum TNF- levels [ 48 ]. TNF-α, IFN-λ, and other proinflammatory cytokines may influence the outcome of leishmaniasis because they play an important role in macrophage activation and activate inducible nitric oxide synthase.…”

The Influence of Single Nucleotide Polymorphisms on Vitamin D Receptor Protein Levels and Function in Chronic Liver Disease

“…The SNPs ApaI and BsmI do not affect the amino acid sequence or structure of the VDR protein because they are located in intron 8 at the 3′ end of the VDR gene. However, the ApaI and BsmI SNPs could affect the alternative splicing of VDR mRNA, alter mRNA stability, and modulate the transcription of the VDR gene [40,41]. The TaqI polymorphism is located in exon 9 at the 3′ end of the human VDR gene and does not alter the VDR protein but causes a synonymous change due to a nucleotide substitution.…”