title: Association between vitamin D metabolism gene polymorphisms and risk of islet autoimmunity and progression to type 1 diabetes: the diabetes autoimmunity study in the young (DAISY).
abstract: BACKGROUND
  Vitamin D metabolism genes have been associated with type 1 diabetes (T1D) risk; however, these genes have not been investigated for association with the preclinical phase of T1D, islet autoimmunity (IA). Studies of vitamin D metabolism genes may elucidate the role of vitamin D in complex diseases.
  
  
  OBJECTIVE
  The objective of the study was to explore the association between seven vitamin D metabolism gene single-nucleotide polymorphisms (SNPs) and the risk of IA and progression to T1D.
  
  
  METHODS
  The Diabetes Autoimmunity Study in the Young is a longitudinal, observational study.
  
  
  METHODS
  Newborn screening for human leukocyte antigen, sibling and offspring recruitment, and follow-up took place in Denver, Colorado.
  
  
  METHODS
  A total of 1708 children at increased genetic risk of T1D participated in the study: 148 developed IA and 62 IA-positive children progressed to T1D.
  
  
  METHODS
  IA, defined as positivity for glutamic acid decarboxylase, insulin, or IA-2 autoantibodies on two or more consecutive visits, and T1D, diagnosed by a physician, were the main outcome measures.
  
  
  RESULTS
  The risk of IA was associated with DHCR7/NADSYN1 rs12785878 and CYP27B1 rs4646536 [hazard ratio 1.36, 95% confidence interval 1.08-1.73 (for each additional minor allele) and hazard ratio 0.59, 95% confidence interval 0.39-0.89 (for A/G compared with the A/A genotype), respectively]. None of the vitamin D SNPs typed was associated with progression to T1D in IA-positive children. Six of the seven SNPs were significantly associated with 25-hydroxyvitamin D levels.
  
  
  CONCLUSIONS
  DHCR7/NADSYN1 rs12785878 and CYP27B1 rs4646536 may play an important role in islet autoimmunity, the preclinical phase of T1D. These findings should be replicated in larger cohorts for confirmation.
authors: MPH, PhD, Colorado School of Public Health, 13001 East 17th Place, Box B119, Aurora, Colorado 80045. jill.norris@ucdenver.edu.
authors: Brittni N
authors: BN
authors: Frederiksen
authors: Miranda
authors: M
authors: Kroehl
authors: Tasha E
authors: TE
authors: Fingerlin
authors: Randall
authors: R
authors: Wong
authors: Andrea K
authors: AK
authors: Steck
authors: Marian
authors: M
authors: Rewers
authors: Jill M
authors: JM
authors: Norris
mesh_terms: D000293:Adolescent; D015551:Autoimmunity / Q000235:genetics / Q000276:immunology; D002648:Child; D002675:Child, Preschool; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics* / Q000276:immunology* / Q000378:metabolism; D018450:Disease Progression; D005260:Female; D005500:Follow-Up Studies; D055106:Genome-Wide Association Study; D006801:Humans; D007223:Infant; D007515:Islets of Langerhans / Q000276:immunology; D008297:Male; D020641:Polymorphism, Single Nucleotide; D011446:Prospective Studies; D012307:Risk Factors; D014807:Vitamin D / Q000235:genetics* / Q000276:immunology* / Q000378:metabolism
chemical_list: D014807:Vitamin D
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