title: Reduced serum vitamin D-binding protein levels are associated with type 1 diabetes.
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.
  
  
  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.
authors.affiliation: Department of Pathology, University of Florida, Gainesville, Florida, USA.
authors.forename: Dustin
authors.initials: D
authors.lastname: Blanton
authors.forename: Zhao
authors.initials: Z
authors.lastname: Han
authors.forename: Lindsey
authors.initials: L
authors.lastname: Bierschenk
authors.forename: M V Prasad
authors.initials: MV
authors.lastname: Linga-Reddy
authors.forename: Hongjie
authors.initials: H
authors.lastname: Wang
authors.forename: Michael
authors.initials: M
authors.lastname: Clare-Salzler
authors.forename: Michael
authors.initials: M
authors.lastname: Haller
authors.forename: Desmond
authors.initials: D
authors.lastname: Schatz
authors.forename: Courtney
authors.initials: C
authors.lastname: Myhr
authors.forename: Jin-Xiong
authors.initials: JX
authors.lastname: She
authors.forename: Clive
authors.initials: C
authors.lastname: Wasserfall
authors.forename: Mark
authors.initials: M
authors.lastname: Atkinson
mesh_terms: D000293:Adolescent; D000328:Adult; D016022:Case-Control Studies; D002648:Child; D003922:Diabetes Mellitus, Type 1 / Q000097:blood* / Q000378:metabolism; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D020641:Polymorphism, Single Nucleotide; D012189:Retrospective Studies; D014807:Vitamin D / Q000031:analogs & derivatives* / Q000097:blood; D014809:Vitamin D-Binding Protein / Q000097:blood* / Q000378:metabolism; D055815:Young Adult
chemical_list: D014809:Vitamin D-Binding Protein; D014807:Vitamin D; C104450:25-hydroxyvitamin D