Vitamin D Binding Protein Impact on 25-Hydroxyvitamin D Levels under Different Physiologic and Pathologic Conditions

Abstract

There is a high prevalence of vitamin D deficiency worldwide, but how to define vitamin D deficiency is controversial. Currently, the plasma concentration of total 25-hydroxyvitamin D [25(OH)D] is considered an indicator of vitamin D status. The free hormone hypothesis states that protein-bound hormones are inactive while unbound hormones are free to exert biological activity. The majority of circulating 25(OH)D and 1,25(OH)2D is tightly bound to vitamin D binding protein (DBP), 10–15% is bound to albumin, and less than 1% of circulating vitamin D exists in an unbound form. While DBP is relatively stable in most healthy populations, a recent study showed that there are gene polymorphisms associated with race and ethnicity that could alter DBP levels and binding affinity. Furthermore, in some clinical situations, total vitamin D levels are altered and knowing whether DBP is also altered may have treatment implications. The aim of this review is to assess DBP concentration in different physiological and pathophysiological conditions. We suggest that DBP should be considered in the interpretation of 25(OH)D levels.

Behind the scenes of vitamin D binding protein: More than vitamin D binding

“…Although T cells express megalin, cubilin expression in naïve T cells is very low and is not upregulated following T cell activation [110]. In comparison with the megalin-mediated endocytosis in mammary cells and kidney cells [53,111], macropinocytosis of 25(OH)-vitamin D 3 -DBP complexes by T cells is not followed by a conversion to 1.25(OH) 2 -vitamin D 3 . As the physiological concentration of 1,25(OH) 2 -vitamin D 3 is not sufficiently high to affect T cell responses, a significant local production of 1,25(OH) 2 -vitamin D 3 (>1000 pM) is required.…”

“…The remaining fraction of vitamin D is bound to albumin (10e15%), and <1% of circulating vitamin D exists in an unbound form. The free hormone hypothesis states that protein-bound hormones are inactive, while unbound hormones are free to exert biological activity [53]. However in recent years, the free hormone hypothesis has been criticized as the serum concentration of free 1,25(OH) 2 -vitamin D 3 (±10 À13 M) is much lower that the concentration bound to the vitamin D receptor (Kd ¼ 10 À10 M) [54].…”

First 25-hydroxyvitamin D assay for general chemistry analyzers

“…Vitamin D, synthesized in the skin and/or obtained from dietary supplements [7,8], circulates in the bloodstream bound to vitamin D binding protein (DBP) [9,10]. DBP is a glycosylated a-globulin of approximately 58 kDa, product of expression of the GC gene located on human chromosome 4 [11].…”

Çukurova Bölgesinde D vitamini düzeyleri

“…Serum veya plazma 25-hidroksi-D3 [25(OH)D3] düzeyi, D vitamininin besinsel ve fonksiyonel durumunu yansıtan en iyi gösterge olarak kabul edilir. Bunun nedeni; 25(OH) D3'ün uzun yarılanma ömrüne (15 ile 35 gün) sahip olması ve kanda yüksek konsantrasyonlarda bulunmasındandır 1,5,6 .…”