Journal
JOURNAL OF BONE AND MINERAL RESEARCH
Volume 31, Issue 6, Pages 1128-1136Publisher
WILEY
DOI: 10.1002/jbmr.2829
Keywords
VITAMIN D-BINDING PROTEIN; Gc; GENOTYPE; BIOAVAILABLE VITAMIN D; LIQUID CHROMATOGRAPHY-TANDEM MASS SPECTROMETRY
Categories
Funding
- National Institutes of Health (NIH) [K23 DK093556, K24 DK076808, U01 AG047837, U01 DK061022, U01 DK060990, UL1RR024134, UL1TR000003]
- NIDDK [U01DK060990, U01DK060984, U01DK061022, U01DK061021, U01DK061028, U01DK060980, U01DK060963, U01DK060902]
- Perelman School of Medicine, University of Pennsylvania Clinical and Translational Science Award NIH/NCATS [UL1TR000003]
- Johns Hopkins University [UL1 TR-000424]
- University of Maryland GCRC [M01 RR-16500]
- National Center for Advancing Translational Sciences (NCATS) of the NIH [UL1TR000439]
- NIH roadmap for Medical Research
- Michigan Institute for Clinical and Health Research (MICHR) [UL1TR000433]
- University of Illinois, Chicago CTSA [UL1RR029879]
- Tulane University Translational Research in Hypertension and Renal Biology [P30GM103337]
- Kaiser Permanente NIH/NCRR UCSF-CTSI [UL1 RR-024131]
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Studies using vitamin D-binding protein (DBP) concentrations to estimate free and bioavailable vitamin D have increased dramatically in recent years. Combinations of two single-nucleotide polymorphisms (SNPs) produce three major DBP isoforms (Gc1f, Gc1s, and Gc2). A recent study showed that DBP concentrations quantified by liquid chromatography-tandem mass spectrometry (LC-MS/MS) did not differ by race, whereas a widely used monoclonal enzyme-linked immunosorbent assay (ELISA) quantified DBP differentially by isoform, yielding significantly lower DBP concentrations in black versus white individuals. We compared measurements of serum DBP using a monoclonal ELISA, a polyclonal ELISA, and LC-MS/MS in 125 participants in the Chronic Renal Insufficiency Cohort (CRIC). Serum free and bioavailable 25OHD were calculated based on DBP concentrations from these three assays in homozygous participants, and race differences were compared. We confirmed that the monoclonal ELISA quantifies DBP differentially by isoform and showed that the polyclonal ELISA is not subject to this bias. Whereas 9% of the variability in DBP concentrations quantified using either LC-MS/MS or the polyclonal ELISA was explained by genotype, 85% of the variability in the monoclonal ELISA-based measures was explained by genotype. DBP concentrations measured by the monoclonal ELISA were disproportionately lower than LC-MS/MS-based results for Gc1f homozygotes (median difference -67%; interquartile range [IQR] -71%, -64%), 95% of whom were black. In contrast, the polyclonal ELISA yielded consistently and similarly higher measurements of DBP than LC-MS/MS, irrespective of genotype, with a median percent difference of +50% (IQR +33%, +65%). Contrary to findings using the monoclonal ELISA, DBP concentrations did not differ by race, and free and bioavailable 25OHD were significantly lower in black versus white participants based on both the polyclonal ELISA and LC-MS/MS, consistent with their lower total 25OHD. Future studies of DBP and free or bioavailable vitamin D metabolites should employ DBP assays that are not biased by DBP genotype. (c) 2016 American Society for Bone and Mineral Research.
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