Plasma 25-Hydroxyvitamin D concentration and risk of islet autoimmunity

Research output: Contribution to journalArticle


We examined the association between plasma 25- hydroxyvitamin D [25(OH)D] concentration and islet autoimmunity (IA) and whether vitamin D gene polymorphisms modify the effect of 25(OH)D on IA risk. We followed 8,676 children at increased genetic risk of type 1 diabetes at six sites in the U.S. and Europe. We defined IA as positivity for at least one autoantibody (GADA, IAA, or IA-2A) on two or more visits. We conducted a risk set sampled nested casecontrol study of 376 IA case subjects and up to 3 control subjects per case subject. 25(OH)D concentrationwas measured on all samples prior to, and including, the first IA positive visit. Nine polymorphisms in VDR, CYP24A, CYP27B1, GC, and RXRA were analyzed as effect modifiers of 25(OH)D. Adjusting for HLA-DR-DQ and ancestry, higher childhood 25(OH)D was associated with lower IA risk (odds ratio = 0.93 for a 5 nmol/L difference; 95% CI 0.89, 0.97). Moreover, this association was modified by VDR rs7975232 (interaction P = 0.0072), where increased childhood 25(OH)D was associated with a decreasing IA risk based upon number of minor alleles: 0 (1.00; 0.93, 1.07), 1 (0.92; 0.89, 0.96), and 2 (0.86; 0.80, 0.92). Vitamin D and VDR may have a combined role in IA development in children at increased genetic risk for type 1 diabetes.


  • Jill M. Norris
  • Hye Seung Lee
  • Brittni Frederiksen
  • Iris Erlund
  • Ulla Uusitalo
  • Jimin Yang
  • Åke Lernmark
  • Olli Simell
  • Jorma Toppari
  • Marian Rewers
  • Anette G. Ziegler
  • Jin Xiong She
  • Suna Onengut-Gumuscu
  • Wei Min Chen
  • Stephen S. Rich
  • Jouko Sundvall
  • Beena Akolkar
  • Jeffrey Krischer
  • Suvi M. Virtanen
  • William Hagopian
External organisations
  • Colorado School of Public Health
  • University of South Florida
  • Finnish National Institute for Health and Welfare
  • Turku University Hospital
  • University of Turku
  • University of Colorado
  • University of Virginia
  • National Institute of Diabetes and Digestive and Kidney Diseases
  • University of Tampere
  • Pacific Northwest Diabetes Research Institute
  • German Diabetes Research Institute
  • Augusta University
Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Endocrinology and Diabetes
Original languageEnglish
Pages (from-to)146-154
Number of pages9
Issue number1
Publication statusPublished - 2018
Publication categoryResearch