TY - JOUR
T1 - Plasma 25-Hydroxyvitamin D concentration and risk of islet autoimmunity
AU - Norris, Jill M.
AU - Lee, Hye Seung
AU - Frederiksen, Brittni
AU - Erlund, Iris
AU - Uusitalo, Ulla
AU - Yang, Jimin
AU - Lernmark, Åke
AU - Simell, Olli
AU - Toppari, Jorma
AU - Rewers, Marian
AU - Ziegler, Anette G.
AU - She, Jin-Xiong
AU - Onengut-Gumuscu, Suna
AU - Chen, Wei Min
AU - Rich, Stephen S.
AU - Sundvall, Jouko
AU - Akolkar, Beena
AU - Krischer, Jeffrey
AU - Virtanen, Suvi M.
AU - Hagopian, William
N1 - Funding Information:
Funding. This work is funded by the National Institute of Diabetes and Digestive and Kidney Diseases (U01 DK63829, U01 DK63861, U01 DK63821, U01 DK63865, U01 DK63863, U01 DK63836, U01 DK63790, UC4 DK63829, UC4 DK63861, UC4 DK63821, UC4 DK63865, UC4 DK63863, UC4 DK63836, UC4 DK95300, UC4 DK100238, UC4 DK106955, and contract no. HHSN267200700014C), National Institute of Allergy and Infectious Diseases, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institute of Environmental Health Sciences, JDRF, and Centers for Disease Control and Prevention. This work was supported in part by the National Institutes of Health National Center for Advancing Translational Sciences Clinical and Translational Science Awards to the University of Florida (UL1 TR000064) and the University of Colorado (UL1 TR001082).
Publisher Copyright:
© 2017 by the American Diabetes Association..
PY - 2018/1/1
Y1 - 2018/1/1
N2 - 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.
AB - 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.
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U2 - 10.2337/db17-0802
DO - 10.2337/db17-0802
M3 - Article
C2 - 29061729
AN - SCOPUS:85038957886
SN - 0012-1797
VL - 67
SP - 146
EP - 154
JO - Diabetes
JF - Diabetes
IS - 1
ER -
