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Norris, J.M.* ; Lee, H.S.* ; Frederiksen, B.* ; Erlund, I.* ; Uusitalo, U.* ; Yang, J.A.* ; Lernmark, A.* ; Simell, O.* ; Toppari, J.* ; Rewers, M.* ; TEDDY Study Group (Ziegler, A.-G.) ; She, J.X.* ; Onengut-Gumuscu, S.* ; Chen, W.M.* ; Rich, S.S.* ; Sundvall, J.* ; Akolkar, B.* ; Krischer, J.* ; Virtanen, S.M.* ; Hagopian, W.*

Plasma 25-hydroxyvitamin D concentration and risk of islet autoimmunity.

Diabetes 67, 146-154 (2018)

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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,andwere 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 byrs7975232 (interaction= 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 andmay have a combined role in IA development in children at increased genetic risk for type 1 diabetes.

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