Reduced Serum Vitamin D-Binding Protein Levels Are Associated With Type 1 Diabetes

  1. Mark Atkinson1
  1. 1Department of Pathology, University of Florida, Gainesville, Florida
  2. 2Center for Biotechnology and Genomic Medicine, Georgia Health Sciences University, Augusta, Georgia
  3. 3Department of Pediatrics, University of Florida, Gainesville, Florida
  1. Corresponding author: Mark Atkinson, atkinson{at}ufl.edu.

Abstract

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.

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  1. Diabetes
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