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- Title
Plasma 25-Hydroxyvitamin D Concentration and Risk of Islet Autoimmunity.
- Authors
Norris, Jill M.; Hye-Seung Lee; Frederiksen, Brittni; Erlund, Iris; Uusitalo, Ulla; Jimin Yang; Lernmark, Åke; Simell, Olli; Toppari, Jorma; Rewers, Marian; Ziegler, Anette-G.; Jin-Xiong She; Onengut-Gumuscu, Suna; Wei-Min Chen; Rich, Stephen S.; Sundvall, Jouko; Akolkar, Beena; Krischer, Jeffrey; Virtanen, Suvi M.; Hagopian, William
- 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 case-control study of 376 IA case subjects and up to 3 control subjects per case subject. 25(OH)D concentration was 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.
- Subjects
TYPE 1 diabetes; AUTOIMMUNITY; GENETIC polymorphisms; CASE-control method; GENETICS; DIABETES risk factors; DISEASE susceptibility; IMMUNITY; RESEARCH funding; VITAMIN D
- Publication
Diabetes, 2018, Vol 67, Issue 1, p146
- ISSN
0012-1797
- Publication type
journal article
- DOI
10.2337/db17-0802