Reduced Serum Vitamin D-Binding Protein Levels Are Associated With Type 1 Diabetes
- Dustin Blanton1,
- Zhao Han1,
- Lindsey Bierschenk1,
- M.V. Prasad Linga-Reddy2,
- Hongjie Wang2,
- Michael Clare-Salzler1,
- Michael Haller3,
- Desmond Schatz3,
- Courtney Myhr1,
- Jin-Xiong She2,
- Clive Wasserfall1 and
- Mark Atkinson1⇓
- 1Department of Pathology, University of Florida, Gainesville, Florida
- 2Center for Biotechnology and Genomic Medicine, Georgia Health Sciences University, Augusta, Georgia
- 3Department of Pediatrics, University of Florida, Gainesville, Florida
- Corresponding author: Mark Atkinson, .
OBJECTIVE Previous studies have noted a specific association between type 1 diabetes and insufficient levels of vitamin D, as well as polymorphisms within genes related to vitamin D pathways. Here, we examined whether serum levels or genotypes of the vitamin D-binding protein (VDBP), a molecule key to the biologic actions of vitamin D, specifically associate with the disorder.
RESEARCH DESIGN AND METHODS A retrospective, cross-sectional analysis of VDBP levels used samples from 472 individuals of similar age and sex distribution, including 153 control subjects, 203 patients with type 1 diabetes, and 116 first-degree relatives of type 1 diabetic patients. Single nucleotide polymorphism (SNP) typing for VDBP polymorphisms (SNP rs4588 and rs7041) was performed on this cohort to determine potential genetic correlations. In addition, SNP analysis of a second sample set of banked DNA samples from 1,502 type 1 diabetic patients and 1,880 control subjects also was used to determine genotype frequencies.
RESULTS Serum VDBP levels were highest in healthy control subjects (median 423.5 µg/mL [range 193.5–4,345.0; interquartile range 354.1–586]), intermediate in first-degree relatives (402.9 µg/mL [204.7–4,850.0; 329.6–492.4]), and lowest in type 1 diabetic patients (385.3 µg/mL [99.3–1,305.0; 328.3–473.0]; P = 0.003 vs. control subjects). VDBP levels did not associate with serum vitamin D levels, age, or disease duration. However, VDBP levels were, overall, lower in male subjects (374.7 µg/mL [188.9–1,602.0; 326.9–449.9]) than female subjects (433.4 µg/mL [99.3–4,850.0; 359.4–567.8]; P < 0.0001). It is noteworthy that no differences in genotype frequencies of the VDBP polymorphisms were associated with serum VDBP levels or between type 1 diabetic patients and control subjects.
CONCLUSIONS Serum VDBP levels are decreased in those with type 1 diabetes. These studies suggest that multiple components in the metabolic pathway of vitamin D may be altered in type 1 diabetes and, collectively, have the potential to influence disease pathogenesis.
- Received April 30, 2011.
- Accepted July 5, 2011.
- © 2011 by the American Diabetes Association.
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