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Plasma concentrations of 25-Hydroxy-Vitamin D and 1,25-Dihydroxy-Vitamin D are Related to the Phenotype of Gc (Vitamin D-Binding Protein): A Cross-sectional Study on 595 Early Postmenopausal Women

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Abstract

The major transporter of vitamin D metabolites in the circulation is the multifunctional plasma protein Gc, also known as group-specific component, Gc globulin, vitamin D–binding protein, or DBP. There are several phenotypes of Gc, and we examined the influence of Gc phenotype and Gc concentration on vitamin D status. By using isoelectric focusing we identified the Gc phenotype of 595 caucasian recent postmenopausal women enrolled into the Danish Osteoporosis Prevention Study (DOPS). We measured plasma concentration of Gc by immunonephelometry (coefficient of variation [CV] < 5%), 25-hydroxy vitamin D (25OHD) by a competitive protein-binding assay (CV 10%), and 1,25-dihydroxy-vitamin D (1,25(OH)2D) by a radioimmunoassay (CV 6–14%), and calculated index as the molar ratio of vitamin concentration divided by Gc concentration. Plasma levels of Gc, 25OHD, 25OHD index, and 1,25(OH)2D, but not 1,25(OH)2D index, differed significantly between women with different Gc phenotype, being highest in Gc1-1, intermediate in Gc1-2, and lowest in Gc2-2. In multiple regression analysis, Gc concentration was an independent predictor of 1,25(OH)2D, whereas Gc phenotype was a significant predictor of 25OHD concentration, even after adjustment for the effects of season, sunbathing habits, skin thickness, use of vitamin supplements, smoking, and body mass index (BMI). Plasma parathyroid hormone (PTH) level did not differ between Gc phenotypes. Despite the fact that more than 60% of the women with Gc phenotype Gc2-2 had plasma 25OHD levels of less than 50 nmol/L none of them had plasma PTH higher than reference limits. Bone mineral content (BMC), Bone mineral density (BMD), and bone markers did not differ between Gc phenotypes. In conclusion, plasma 1,25(OH)2D, 25OHD, and 25OHD index are related to Gc phenotype, and we speculate that the thresholds for vitamin D sufficiency differ between Gc phenotypes.

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Acknowledgment

Our study was supported by research grants from “Karen Elise Jensens Fond”, “Th Maigaards Eftf Fru Lily Benthine Lunds Fond af 1/6-78”, “PA Messerschmidt og Hustrus Fond til udforskning og bekempelse af sygdomme”, “Beckett-fonden”, “Aarhus Universitetshospitals Forskningsinitiativ”, “Aarhus Universitets Forskningsfond” and Clinical Institute, Aarhus University, Denmark.

We are grateful to Mariann Thymann (Institute of Forensic Science, University of Copenhagen, Copenhagen, Denmark) for the gift of control serum samples of each Gc phenotype, and to Irene Molbo, Inger Nygaard, and Inger Marie Jensen for their technical assistance.

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Correspondence to A. L. Lauridsen.

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Lauridsen, A.L., Vestergaard, P., Hermann, A.P. et al. Plasma concentrations of 25-Hydroxy-Vitamin D and 1,25-Dihydroxy-Vitamin D are Related to the Phenotype of Gc (Vitamin D-Binding Protein): A Cross-sectional Study on 595 Early Postmenopausal Women. Calcif Tissue Int 77, 15–22 (2005). https://doi.org/10.1007/s00223-004-0227-5

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