Free 25-Hydroxyvitamin D: Impact of Vitamin D Binding Protein Assays on Racial-Genotypic Associations

Carrie M Nielson, Kerry S Jones, Rene F Chun, Jon M Jacobs, Ying Wang, Martin Hewison, John S Adams, Christine M Swanson, Christine G Lee, Dirk Vanderschueren, Steven Pauwels, Ann Prentice, Richard D Smith, Tujin Shi, Yuqian Gao, Athena A Schepmoes, Joseph M Zmuda, Jodi Lapidus, Jane A Cauley, Roger BouillonInez Schoenmakers, Eric S Orwoll, Osteoporotic Fractures in Men (MrOS) Research Group

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Context: Total 25-hydroxyvitamin D (25OHD) is a marker of vitamin D status and is lower in African Americans than in whites. Whether this difference holds for free 25OHOD (f25OHD) is unclear, considering reported genetic-racial differences in vitamin D binding protein (DBP) used to calculate f25OHD. 

Objectives: Our objective was to assess racial-geographic differences in f25OHD and to understand inconsistencies in racial associations with DBP and calculated f25OHD. 

Design: This study used a cross-sectional design. 

Setting: The general community in the United States, United Kingdom, and The Gambia were included in this study. 

Participants: Men in Osteoporotic Fractures in Men and Medical Research Council studies (N = 1057) were included. 

Exposures: Total 25OHD concentration, race, and DBP (GC) genotype exposures were included. 

Outcome Measures: Directly measured f25OHD, DBP assessed by proteomics, monoclonal and polyclonal immunoassays, and calculated f25OHD were the outcome measures. 

Results: Total 25OHD correlated strongly with directly measured f25OHD (Spearman r = 0.84). Measured by monoclonal assay, mean DBP in African-ancestry subjects was approximately 50% lower than in whites, whereas DBP measured by polyclonal DBP antibodies or proteomic methods was not lower in African-ancestry. Calculated f25OHD (using polyclonal DBP assays) correlated strongly with directly measured f25OHD (r = 0.80–0.83). Free 25OHD, measured or calculated from polyclonal DBP assays, reflected total 25OHD concentration irrespective of race and was lower in African Americans than in US whites. 

Conclusions: Previously reported racial differences in DBP concentration are likely from monoclonal assay bias, as there was no racial difference in DBP concentration by other methods. This confirms the poor vitamin D status of many African-Americans and the utility of total 25OHD in assessing vitamin D in the general population. 

Original languageEnglish
Pages (from-to)2226-34
Number of pages9
JournalJournal of Clinical Endocrinology & Metabolism
Issue number5
Early online date23 Mar 2016
Publication statusPublished - 1 May 2016

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