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

J Clin Endocrinol Metab. 2016 May;101(5):2226-34. doi: 10.1210/jc.2016-1104. Epub 2016 Mar 23.

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.

MeSH terms

  • Adult
  • African Continental Ancestry Group
  • Aged
  • Cross-Sectional Studies
  • European Continental Ancestry Group
  • Humans
  • Male
  • Vitamin D / analogs & derivatives*
  • Vitamin D / blood
  • Vitamin D-Binding Protein / blood*

Substances

  • Vitamin D-Binding Protein
  • Vitamin D
  • 25-hydroxyvitamin D