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

Research output: Contribution to journalArticlepeer-review

28 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)146-154
Number of pages9
JournalDiabetes
Volume67
Issue number1
DOIs
StatePublished - Jan 1 2018

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism

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