# Common Genetic Variation of Vitamin D Binding Protein and Vitamin D Kinetics

> **NIH NIH F32** · UNIVERSITY OF WASHINGTON · 2021 · $62,671

## Abstract

PROJECT SUMMARY/ABSTRACT
Vitamin D binding protein (DBP) stabilizes circulating concentrations of vitamin D metabolites and modulates
their delivery to tissues. Many observational studies have linked common genetic variants of DBP to risk for
disease. Other studies have found these same genetic variants modify the relationship between serum total
25-hydroxyvitamin D (25OHD) concentration and disease outcomes. Of interest, these variants of DBP are
associated with ancestry and may underlie a portion of the racial heterogeneity in total 25OHD-disease
associations. Few studies have investigated how this variation of DBP affects vitamin D metabolism and
activity. The goal of this project is to identify mechanisms through which common genetic variants of DBP
affect vitamin D metabolism. A plausible mechanism or mediating factor is the serum free fraction of 25OHD
(percent free 25OHD). Pharmacokinetic principles predict that serum DBP concentration and 25OHD-DBP
binding affinity will determine the percent free 25OHD, which will influence tissue availability and clearance of
25OHD. This study seeks to substantiate these predictions. The first research aim is to quantify the association
between percent free 25OHD and 25OHD metabolic clearance. We will pursue this aim within a large stable
isotope tracer study of 25OHD clearance that included adults of Black or White race. For this project, serum
free 25OHD concentration will be directly measured in baseline samples with a novel liquid chromatography-
tandem mass spectrometry method. I expect the percent free 25OHD to be positively related to 25OHD
metabolic clearance and to mediate associations of clearance with race and DBP genotype. The second aim is
to quantify associations of DBP genotypes with the percent free 25OHD and the serum 25OHD and PTH
responses to vitamin D supplementation. We will pursue this aim within a randomized controlled trial of vitamin
D supplementation nested in the Multi-Ethnic Study of Atherosclerosis (MESA), an ethnically diverse cohort of
U.S. adults. Serum concentrations of free 25OHD will be measured at baseline and follow-up. I expect the
percent free 25OHD to differ by DBP genotype, and I hypothesize that DBP genotype influences 25OHD
clearance, therefore modifies the serum total 25OHD response to supplementation but does not modify the
free 25OHD or PTH response. In summary, this project will determine whether and to what extent common
genetic variation of DBP is associated with percent free 25OHD, 25OHD clearance, and the 25OHD and PTH
responses to vitamin D supplementation. Anticipated results include a mechanistic explanation for a portion of
the heterogeneity in associations between serum total 25OHD concentration and health outcomes. Knowledge
generated by this work may contribute to discovery of more generalizable biomarkers of vitamin D status. This
project will provide me with mentored training in concepts and approaches germane to the study of vitamin D
biology, ...

## Key facts

- **NIH application ID:** 10312257
- **Project number:** 1F32DK128864-01A1
- **Recipient organization:** UNIVERSITY OF WASHINGTON
- **Principal Investigator:** CORA M BEST
- **Activity code:** F32 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $62,671
- **Award type:** 1
- **Project period:** 2021-09-03 → 2022-08-08

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10312257

## Citation

> US National Institutes of Health, RePORTER application 10312257, Common Genetic Variation of Vitamin D Binding Protein and Vitamin D Kinetics (1F32DK128864-01A1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10312257. Licensed CC0.

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