Association of Vitamin D Receptor Gene Polymorphisms with Serum Vitamin D Levels in a Greek Rural Population (Velestino Study)

Abstract

<b><i>Background/Aim:</i></b> An alarming increase in vitamin D deficiency even in sunny regions highlights the need for a better understanding of the genetic background of the vitamin D endocrine system and the molecular mechanisms of gene polymorphisms of the vitamin D receptor (VDR). In this study, the serum levels of 25(OH)D<sub>3</sub> were correlated with common VDR polymorphisms (<i>ApaI, BsmI, FokI</i>, and <i>TaqI</i>) in 98 subjects of a Greek homogeneous rural population. <b><i>Methods:</i></b> 25(OH)D<sub>3</sub> concentration was measured by ultra-HPLC, and the VDR gene polymorphisms were identified by quantitative real-time PCR followed by amplicon high-resolution melting analysis. <b><i>Results:</i></b> Subjects carrying either the B <i>BsmI</i> (OR: 0.52, 95% CI: 0.27–0.99) or t <i>TaqI</i> (OR: 2.06, 95%: 1.06–3.99) allele presented twice the risk for developing vitamin D deficiency compared to the reference allele. Moreover, subjects carrying 1, 2, or all 3 of these genotypes (BB/Bb, Tt/tt, and FF) demonstrated 2-fold (OR: 2.04, 95% CI: 0.42–9.92), 3.6-fold (OR: 3.62, 95% CI: 1.07–12.2), and 7-fold (OR: 6.92, 95% CI: 1.68–28.5) increased risk for low 25(OH)D<sub>3</sub> levels, respectively. <b><i>Conclusions:</i></b> Our findings reveal a cumulative effect of specific VDR gene polymorphisms that may regulate vitamin D concentrations explaining, in part, the paradox of vitamin D deficiency in sunny regions, with important implications for precision medicine.

Vitamin D Receptor Gene Polymorphism and Vitamin D Status in Population of Patients with Cardiovascular Disease—A Preliminary Study

“…Although the relationship between VDR polymorphism and 25(OH)D levels was confirmed, the mechanism of this linkage is unknown [33]. Divanoglou et al [34] suggested that epigenetic modifications of VDR regulate the conversion of vitD into its metabolites through CYP450 and thus affect 25(OH)D concentrations.…”

Vitamin D Status and Its Relationship with Age, Gender and Parathyroid Hormone

“…It explains why women suffer more from vitamin D deficiency (Arosio et al, 2020). Findings from other authors in this field, reveal a cumulative effect of specific VDR gene polymorphisms that may regulate vitamin D concentrations explaining, in part, the paradox of vitamin D deficiency in sunny regions, with important implications for precision medicine (Divanoglou et al, 2021). Parathyroid gland abnormalities/or linked diseases, as we can see from the graph affect the level of vitamin D in this group.…”

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 ].…”

“…The functional impact of this polymorphism has not yet been clearly described. These polymorphisms are strictly correlated to diseases and changes in homeostasis processes, such as bone mineralization and calcium intake [ 81 , 82 , 84 ]. For example, the VDR gene can interact with calcium in humans [ 83 ].…”