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

Pegah Yousefzadeh, Sue A Shapses, Xiangbing Wang, Pegah Yousefzadeh, Sue A Shapses, Xiangbing Wang

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.

References

    1. Holick MF. Resurrection of vitamin D deficiency and rickets. The Journal of Clinical Investigation. 2006;116(8):2062–2072.
    1. Mendel CM. The free hormone hypothesis: a physiologically based mathematical model. Endocrine Reviews. 1989;10(3):232–274.
    1. Bikle DD, Siiteri PK, Ryzen E. Serum protein binding of 1,25-dihydroxyvitamin D: a reevaluation by direct measurement of free metabolite levels. The Journal of Clinical Endocrinology & Metabolism. 1985;61(5):969–975.
    1. Chun RF, Peercy BE, Orwoll ES, Nielson CM, Adams JS, Hewison M. Vitamin D and DBP: the free hormone hypothesis revisited. The Journal of Steroid Biochemistry and Molecular Biology. 2013
    1. Powe CE, Evans MK, Wenger J, Zonderman AB, Berg AH, Nalls M, et al. Vitamin D-binding protein and vitamin D status of black Americans and white Americans. The New England Journal of Medicine. 2013;369(21):1991–2000.
    1. Schwartz JB, Lai J, Lizaola B, et al. A comparison of direct and calculated free 25(OH) Vitamin D levels in clinical populations. The Journal of Clinical Endocrinology & Metabolism. 2014
    1. Vermeulen A, Verdonck L, Kaufman JM. A critical evaluation of simple methods for the estimation of free testosterone in serum. The Journal of Clinical Endocrinology & Metabolism. 1999;84(10):3666–3672.
    1. Bikle DD, Gee E, Halloran B, Haddad JG. Free 1,25-dihydroxyvitamin D levels in serum from normal subjects, pregnant subjects, and subjects with liver disease. The Journal of Clinical Investigation. 1984;74(6):1966–1971.
    1. Blanton D, Han Z, Bierschenk L, et al. Reduced serum vitamin D-binding protein levels are associated with type 1 diabetes. Diabetes. 2011;60(10):2566–2570.
    1. Stokes CS, Volmer DA, Grünhage F, Lammert F. Vitamin D in chronic liver disease. Liver International. 2013;33(3):338–352.
    1. Denburg MR, Kalkwarf HJ, de Boer IH, Hewison M, Shults J, Zemel BS, et al. Vitamin D bioavailability and catabolism in pediatric chronic kidney disease. Pediatric Nephrology. 2013;28(9):1843–1853.
    1. Møller UK, Streym S, Heickendorff L, Mosekilde L, Rejnmark L. Effects of 25(OH)D concentrations on chances of pregnancy and pregnancy outcomes: a cohort study in healthy Danish women. European Journal of Clinical Nutrition. 2012;66:862–868.
    1. Moller UK, Streym SV, Jensen LT, et al. Increased plasma concentrations of vitamin D metabolites and vitamin D binding protein in women using hormonal contraceptives: a cross-sectional study. Nutrients. 2013;5(9):3470–3480.
    1. Dastani Z, Berger C, Langsetmo L, Fu L, Wong BY, Malik S, et al. In healthy adults, biological activity of vitamin D, as assessed by serum PTH, is largely independent of DBP concentrations. Journal of Bone and Mineral Research. 2014;29(2):494–499.
    1. Nesby-O’Dell S, Scanlon KS, Cogswell ME, et al. Hypovitaminosis D prevalence and determinants among African American and white women of reproductive age: third National Health and Nutrition Examination Survey, 1988–1994. American Journal of Clinical Nutrition. 2002;76(1):187–192.
    1. Engelman CD, Fingerlin TE, Langefeld CD, et al. Genetic and environmental determinants of 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D levels in hispanic and African Americans. The Journal of Clinical Endocrinology & Metabolism. 2008;93(9):3381–3388.
    1. Wang TJ, Zhang F, Richards JB, et al. Common genetic determinants of vitamin D insufficiency: a genome-wide association study. . The Lancet. 2010;376(9736):180–188.
    1. Levin GP, Robinson-Cohen C, De Boer IH, Houston DK, Lohman K, Liu Y, et al. Genetic variants and associations of 25-hydroxyvitamin D concentrations with major clinical outcomes. The Journal of the American Medical Association. 2012;308(18):1898–1905.
    1. Santos BR, Mascarenhas LP, Boguszewski MC, Spritzer PM. Variations in the vitamin D-binding protein (DBP) gene are related to lower 25-hydroxyvitamin D levels in healthy girls: a cross-sectional study. Hormone Research in Paediatrics. 2013;79:162–168.
    1. Cheung CL, Lau KS, Sham PC, Tan KC, Kung AW. Genetic variant in vitamin D binding protein is associated with serum 25-hydroxyvitamin D and vitamin D insufficiency in southern Chinese. Journal of Human Genetics. 2013;58:749–751.
    1. Wang X, Shapses SA. Vitamin D binding protein levels in normal pre-and post menopausal women. Endocrine Reviews. 2013;34
    1. Carpenter TO, Zhang JH, Parra E, Ellis BK, Simpson C, Lee WM. Vitamin D binding protein is a key determinant of 25-hydroxyvitamin D levels in infants and toddlers. Journal of Bone and Mineral Research. 2013;28(1):213–221.
    1. Perna L, Felix JF, Breitling LP, et al. Genetic variations in the vitamin D binding protein and season-specific levels of vitamin D among older adults. Epidemiology. 2013;24(1):104–109.
    1. Winters SJ, Chennubhatla R, Wang C, Miller JJ. Influence of obesity on vitamin D-binding protein and 25-hydroxy vitamin D levels in African American and white women. Metabolism: Clinical and Experimental. 2009;58(4):438–442.
    1. Bolland MJ, Grey AB, Ames RW, et al. Age-, gender-, and weight-related effects on levels of 25-hydroxyvitamin D are not mediated by vitamin D binding protein. Clinical Endocrinology. 2007;67(2):259–264.
    1. Schwartz JB, Lai J, Lizaola B, et al. Variability in free 25(OH) vitamin D levels in clinical populations. The Journal of Steroid Biochemistry and Molecular Biology. 2013
    1. Bouillon R, van Assche FA, van Baelen H, Heyns W, de Moor P. Influence of the vitamin D-binding protein on the serum concentration of 1,25-dihydroxyvitamin D3. Significance of the free 1,25-dihydroxyvitamin D3 concentration. The Journal of Clinical Investigation. 1981;67(3):589–596.
    1. Egawa T, Ito H, Nakamura H, Yamamoto H, Kishimoto S. Hormonal regulation of vitamin D-binding protein production by a human hepatoma cell line. Biochemistry International. 1992;28(3):551–557.
    1. Rejnmark L, Lauridsen AL, Brot C, et al. Vitamin D and its binding protein Gc: long-term variability in peri- and postmenopausal women with and without hormone replacement therapy. Scandinavian Journal of Clinical and Laboratory Investigation. 2006;66(3):227–238.
    1. Ashraf AP, Huisingh C, Alvarez JA, Wang X, Gower BA. Insulin resistance indices are inversely associated with vitamin D binding protein concentrations. The Journal of Clinical Endocrinology & Metabolism. 2014;99(1):178–183.
    1. Karlsson T, Osmancevic A, Jansson N, Hulthén L, Holmäng A, Larsson I. Increased vitamin D-binding protein and decreased free 25(OH)D in obese women of reproductive age. European Journal of Nutrition. 2014;53(1):259–267.
    1. Malham M, Jørgensen SP, Ott P, et al. Vitamin D deficiency in cirrhosis relates to liver dysfunction rather than aetiology. World Journal of Gastroenterology. 2011;17(7):922–925.
    1. Corey RL, Whitaker MD, Crowell MD, Keddis MT, Aqel B, Balan V, et al. Vitamin D deficiency, parathyroid hormone (PTH) levels, and bone disease among patients with end stage liver disease (ESLD) and normal serum creatinine awaiting liver transplantation (LT) Clinical Transplantation. 2014
    1. Reese PP, Bloom RD, Feldman HI, et al. Changes in vitamin D binding protein and vitamin D concentrations associated with liver transplantation. Liver International. 2012;32(2):287–296.
    1. Colston K, Williams NJ, Cleeve HJW. Studies on vitamin D binding protein in the nephrotic syndrome. Clinical Chemistry. 1985;31(5):718–721.
    1. Vilasi A, Cutillas PR, Maher AD, et al. Combined proteomic and metabonomic studies in three genetic forms of the renal Fanconi syndrome. American Journal of Physiology—Renal Physiology. 2007;293(2):F456–F467.
    1. Doorenbos CRC, de Cuba MM, Vogt L, et al. Antiproteinuric treatment reduces urinary loss of vitamin D-binding protein but does not affect vitamin D status in patients with chronic kidney disease. Journal of Steroid Biochemistry and Molecular Biology. 2012;128(1-2):56–61.
    1. Mirkovic K, Doorenbos CR, Dam WA, Lambers Heerspink HJ, Slagman MC, Nauta FL, et al. Urinary vitamin D binding protein: a potential novel marker of renal interstitial inflammation and fibrosis. PLoS ONE. 2013;8e55887
    1. Bhan I, Powe CE, Berg AH, et al. Bioavailable vitamin D is more tightly linked to mineral metabolism than total vitamin D in incident hemodialysis patients. Kidney International. 2012;82:84–89.
    1. Thrailkill KM, Jo C-H, Cockrell GE, Moreau CS, Fowlkes JL. Enhanced excretion of vitamin D binding protein in type 1 diabetes: a role in vitamin D deficiency? The Journal of Clinical Endocrinology & Metabolism. 2011;96(1):142–149.
    1. Tian XQ, Zhao LM, Ge JP, Zhang Y, Xu YC. Elevated urinary level of vitamin D-binding protein as a novel biomarker for diabetic nephropathy. Experimental and Therapeutic Medicine. 2014;7(2):411–416.
    1. Clements MR, Davies M, Hayes ME, et al. The role of 1,25-dihydroxyvitamin D in the mechanism of acquired vitamin D deficiency. Clinical Endocrinology. 1992;37(1):17–27.
    1. Wang X, Shapses SA, Wei S, Sukumar D, Ghosh J. Vitamin D binding protein levels in female patients with primary hyperparathyroidism. Endocrine Practice. 2013;19(4):609–613.
    1. Yin L, Ordóñez-Mena JM, Chen T, Schöttker B, Arndt V, Brenner H. Circulating 25-hydroxyvitamin D serum concentration and total cancer incidence and mortality: a systematic review and meta-analysis. Preventive Medicine. 2013;57(6):753–764.
    1. Weinstein SJ, Stolzenberg-Solomon RZ, Kopp W, Rager H, Virtamo J, Albanes D. Impact of circulating vitamin D binding protein levels on the association between 25-hydroxyvitamin d and pancreatic cancer risk: a nested case-control study. Cancer Research. 2012;72(5):1190–1198.
    1. Weinstein SJ, Mondul AM, Kopp W, Rager H, Virtamo J, Albanes D. Circulating 25-hydroxyvitamin D, vitamin D-binding protein and risk of prostate cancer. International Journal of Cancer. 2013;132(12):2940–2947.
    1. Mondul AM, Weinstein SJ, Virtamo J, Albanes D. Influence of vitamin D binding protein on the association between circulating vitamin D and risk of bladder cancer. British Journal of Cancer. 2012;107(9):1589–1594.
    1. Havens PL, Kiser JJ, Stephensen CB, Hazra R, Flynn PM, Wilson CM, et al. Association of higher plasma vitamin D binding protein and lower free calcitriol levels with tenofovir disoproxil fumarate use and plasma and intracellular tenofovir pharmacokinetics: cause of a functional vitamin d deficiency. Antimicrobial Agents and Chemotherapy. 2013;57(11):5619–5628.
    1. Waldron JL, Ashby HL, Cornes MP, Bechervaise J, Razavi C, Thomas OL, et al. Vitamin D: a negative acute phase reactant. Journal of Clinical Pathology. 2013;66(7):620–622.
    1. Watkins RR, Yamshchikov AV, Lemonovich TL, Salata RA. The role of vitamin D deficiency in sepsis and potential therapeutic implications. Journal of Infection. 2011;63(5):321–326.
    1. Jeng L, Yamshchikov AV, Judd SE, et al. Alterations in vitamin D status and anti-microbial peptide levels in patients in the intensive care unit with sepsis. Journal of Translational Medicine. 2009;7(article 28)
    1. Hiemstra TF, Casian A, Boraks P, Jayne DR, Schoenmakers I. Plasma exchange induces vitamin D deficiency. QJM. 2014;107(2):120–130.
    1. Prytuła A, Wells D, McLean T, et al. Urinary and dialysate losses of vitamin D-binding protein in children on chronic peritoneal dialysis. Pediatric Nephrology. 2012;27(4):643–649.

Source: PubMed

스폰서 및 공동 작업자

건강 상태

약물 개입

3
구독하다