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Plasma 25-Hydroxyvitamin D concentration and risk of islet autoimmunity

  • 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
Publishing year: 2018
Language: English
Pages: 146-154
Publication/Series: Diabetes
Volume: 67
Issue: 1
Document type: Journal article
Publisher: American Diabetes Association Inc.

Abstract english

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.


  • Endocrinology and Diabetes


  • Diabetes and Celiac Unit
  • ISSN: 0012-1797
E-mail: ake [dot] lernmark [at] med [dot] lu [dot] se

Principal investigator

Diabetes and Celiac Unit

+46 40 39 19 01

+46 70 616 47 79


Jan Waldenströms gata 35, Malmö


Lund University Diabetes Centre, CRC, SUS Malmö, Jan Waldenströms gata 35, House 91:12. SE-214 28 Malmö. Telephone: +46 40 39 10 00