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 Bouillon; Inez Schoenmakers; Eric S. Orwoll; Osteoporotic Fractures in Men (MrOS) Research Group

doi:10.1210/jc.2016-1104

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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Abstract

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 language	English
Pages (from-to)	2226-2234
Number of pages	9
Journal	Journal of Clinical Endocrinology & Metabolism
Volume	101
Issue number	5
Early online date	23 Mar 2016
DOIs	https://doi.org/10.1210/jc.2016-1104
Publication status	Published - 1 May 2016

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Nielson, C. M., Jones, K. S., Chun, R. F., Jacobs, J. M., Wang, Y., Hewison, M., Adams, J. S., Swanson, C. M., Lee, C. G., Vanderschueren, D., Pauwels, S., Prentice, A., Smith, R. D., Shi, T., Gao, Y., Schepmoes, A. A., Zmuda, J. M., Lapidus, J., Cauley, J. A., ... Osteoporotic Fractures in Men (MrOS) Research Group (2016). Free 25-hydroxyvitamin D: Impact of vitamin D binding protein assays on racial-genotypic associations. Journal of Clinical Endocrinology & Metabolism, 101(5), 2226-2234. https://doi.org/10.1210/jc.2016-1104

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title = "Free 25-hydroxyvitamin D: Impact of vitamin D binding protein assays on racial-genotypic associations",

abstract = "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. ",

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

note = "This article is published under the terms of the Creative Commons Attribution-Non Commercial License (CC-BY-NC; https://creativecommons.org/licenses/by-nc/4.0/)",

year = "2016",

month = may,

day = "1",

doi = "10.1210/jc.2016-1104",

language = "English",

volume = "101",

pages = "2226--2234",

journal = "Journal of Clinical Endocrinology & Metabolism",

issn = "0021-972X",

publisher = "The Endocrine Society",

number = "5",

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Nielson, CM, Jones, KS, Chun, RF, Jacobs, JM, Wang, Y, Hewison, M, Adams, JS, Swanson, CM, Lee, CG, Vanderschueren, D, Pauwels, S, Prentice, A, Smith, RD, Shi, T, Gao, Y, Schepmoes, AA, Zmuda, JM, Lapidus, J, Cauley, JA, Bouillon, R, Schoenmakers, I, Orwoll, ES & Osteoporotic Fractures in Men (MrOS) Research Group 2016, 'Free 25-hydroxyvitamin D: Impact of vitamin D binding protein assays on racial-genotypic associations', Journal of Clinical Endocrinology & Metabolism, vol. 101, no. 5, pp. 2226-2234. https://doi.org/10.1210/jc.2016-1104

TY - JOUR

T1 - Free 25-hydroxyvitamin D: Impact of vitamin D binding protein assays on racial-genotypic associations

AU - Nielson, Carrie M.

AU - Jones, Kerry S.

AU - Chun, Rene F.

AU - Jacobs, Jon M.

AU - Wang, Ying

AU - Hewison, Martin

AU - Adams, John S.

AU - Swanson, Christine M.

AU - Lee, Christine G.

AU - Vanderschueren, Dirk

AU - Pauwels, Steven

AU - Prentice, Ann

AU - Smith, Richard D.

AU - Shi, Tujin

AU - Gao, Yuqian

AU - Schepmoes, Athena A.

AU - Zmuda, Joseph M.

AU - Lapidus, Jodi

AU - Cauley, Jane A.

AU - Bouillon, Roger

AU - Schoenmakers, Inez

AU - Orwoll, Eric S.

AU - Osteoporotic Fractures in Men (MrOS) Research Group

N1 - This article is published under the terms of the Creative Commons Attribution-Non Commercial License (CC-BY-NC; https://creativecommons.org/licenses/by-nc/4.0/)

PY - 2016/5/1

Y1 - 2016/5/1

N2 - 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.

AB - 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.

U2 - 10.1210/jc.2016-1104

DO - 10.1210/jc.2016-1104

M3 - Article

C2 - 27007693

VL - 101

SP - 2226

EP - 2234

JO - Journal of Clinical Endocrinology & Metabolism

JF - Journal of Clinical Endocrinology & Metabolism

SN - 0021-972X

IS - 5

ER -