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      The variation in free 25-hydroxy vitamin D and vitamin D-binding protein with season and vitamin D status

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          Abstract

          Purpose

          Serum 25-hydroxy vitamin D [25(OH)D] varies greatly with season at northern latitudes. The purpose of this study was to determine if the seasonal variations in serum total 25(OH)D are followed by a concomitant variation in free 25(OH)D or if the variation is damped by alterations in the binding capacity of DBP.

          Methods

          Serum was collected from 540 healthy blood donors (60% men; mean age 41 ± 13 years) during 12 months and analyzed for total 25(OH)D, directly measured free 25(OH)D, vitamin D-binding protein (DBP) and albumin. Calculated free 25(OH)D was estimated.

          Results

          The UV-B radiation during the sampling month was positively correlated with the serum levels of total 25(OH)D ( r = 0.355, P < 0.001), directly measured free ( r = 0.336, P < 0.001) and calculated free 25(OH)D ( r = 0.275, P < 0.001), but not with DBP and albumin. The percentage of free 25(OH)D was higher during the winter months than that during the summer months (0.020 ± 0.005% vs 0.019 ± 0.004%; P = 0.007) and higher in participants with a serum 25(OH)D below 25 nmol/L than that in participants with a serum 25(OH)D above 75 nmol/L (0.031 ± 0.007% vs 0.017 ± 0.003%; P < 0.001). iPTH was correlated with directly measured free 25(OH)D ( r = −0.226; P < 0.001), but only weakly with calculated free 25(OH)D ( r = −0.095; P = 0.027).

          Conclusions

          Directly measured free serum 25(OH)D was highly correlated with total serum 25(OH)D and followed the same seasonal variation, whereas the serum concentrations of DBP and albumin were stable. The fluctuation in free 25(OH)D was only marginally damped with an increase in the percentage of free 25(OH)D during the winter months and in participants with vitamin D deficiency.

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          Most cited references13

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          An endocytic pathway essential for renal uptake and activation of the steroid 25-(OH) vitamin D3.

          Steroid hormones may enter cells by diffusion through the plasma membrane. However, we demonstrate here that some steroid hormones are taken up by receptor-mediated endocytosis of steroid-carrier complexes. We show that 25-(OH) vitamin D3 in complex with its plasma carrier, the vitamin D-binding protein, is filtered through the glomerulus and reabsorbed in the proximal tubules by the endocytic receptor megalin. Endocytosis is required to preserve 25-(OH) vitamin D3 and to deliver to the cells the precursor for generation of 1,25-(OH)2 vitamin D3, a regulator of the calcium metabolism. Megalin-/- mice are unable to retrieve the steroid from the glomerular filtrate and develop vitamin D deficiency and bone disease.
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            Biological and clinical aspects of the vitamin D binding protein (Gc-globulin) and its polymorphism.

            The vitamin D binding protein (DBP) is the major plasma carrier protein of vitamin D and its metabolites. Unlike other hydrophobic hormone-binding systems, it circulates in a considerably higher titer compared to its ligands. Apart from its specific sterol binding capacity, DBP exerts several other important biological functions such as actin scavenging, fatty acid transport, macrophage activation and chemotaxis. The DBP-gene is a member of a multigene cluster that includes albumin, alpha-fetoprotein, and alpha-albumin/afamin. All four genes are expressed predominantly in the liver with overlapping developmental profiles. DBP is a highly polymorphic serum protein with three common alleles (Gc1F, Gc1S and Gc2) and more than 120 rare variants. The presence of unique alleles is a useful tool for anthropological studies to discriminate and to reveal ancestral links between populations. Many studies have discussed the link between DBP-phenotypes and susceptibility or resistance to osteoporosis, Graves' disease, Hashimoto's thyroiditis, diabetes, COPD, AIDS, multiple sclerosis, sarcoidosis and rheumatic fever. This article reviews the general characteristics, functions and clinical aspects of DBP.
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              Seasonal variations in serum 25-hydroxy vitamin D levels in a Swedish cohort

              To study seasonal inter-individual and intra-individual variations in serum 25-hydroxy vitamin D (25(OH)D) and to explore parameters associated with 25(OH)D in a healthy Swedish adult population. 540 blood donors (60 % men; mean age 41 ± 13 years) and 75 thrombocyte donors (92 % men, aged 46 ± 11 years) were included. Serum was collected during 12 months and analyzed for 25(OH)D and parathyroid hormone (S-iPTH). The blood donors answered questionnaires concerning vitamin D supplements, smoking, physical activity, sunbed use and sun holidays. Repeated serum samples were collected from the thrombocyte donors to study the intra-individual variations in S-25(OH)D. S-25(OH)D varied greatly over the year correlating with the intensity of the UV-B irradiation (r S = 0.326; p < 0.001). During January–March, a S-25(OH)D level below the thresholds of 50 and 75 nmol/L was observed in 58 and 88 %, respectively, and during July–September in 11 and 50 % (p < 0.001). S-25(OH)D was negatively correlated with body mass index and S-iPTH, but was significantly higher in holiday makers in sunny destinations, sunbed users, non-smokers, and in the physically active. The intra-individual analyses showed a mean increase in S-25(OH)D by 8 nmol/L/month between April and August. Approximately 75 % had serum 25(OH)D values <75 nmol/L during 75 % of the year and 50 % had serum 25(OH)D <50 nmol/L during 50 % of the year. Serum 25(OH)D was strongly associated with parameters related to sun exposure, but only weakly with intake of vitamin D supplements.

                Author and article information

                Journal
                Endocr Connect
                Endocr Connect
                EC
                Endocrine Connections
                Bioscientifica Ltd (Bristol )
                2049-3614
                January 2017
                08 February 2017
                : 6
                : 2
                : 111-120
                Affiliations
                [1 ]Department of Clinical Chemistry and Transfusion Medicine Sahlgrenska Academy at the University of Gothenburg, Gothenburg, Sweden
                [2 ]Department of Clinical Chemistry Sahlgrenska University Hospital, Gothenburg, Sweden
                [3 ]Department of Rheumatology and Inflammation Research Sahlgrenska Academy at the University of Gothenburg, Gothenburg, Sweden
                Author notes
                Correspondence should be addressed to E Klingberg; Email: Eva.Klingberg@ 123456vgregion.se
                Article
                EC160078
                10.1530/EC-16-0078
                5428908
                28179376
                e4bc48f9-4901-4e0f-8231-a866da5581e1
                © 2017 The authors

                This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License .

                History
                : 20 December 2016
                : 8 February 2017
                Categories
                Research

                free 25-hydroxy vitamin d,vitamin d-binding protein,25-hydroxy vitamin d,vitamin d deficiency,parathyroid hormone

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