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)D₃ 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)D₃ 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)D₃ 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.