Norris Jill M, Lee Hye-Seung, Frederiksen Brittni, Erlund Iris, Uusitalo Ulla, Yang Jimin, Lernmark Åke, Simell Olli, Toppari Jorma, Rewers Marian, Ziegler Anette-G, She Jin-Xiong, Onengut-Gumuscu Suna, Chen Wei-Min, Rich Stephen S, Sundvall Jouko, Akolkar Beena, Krischer Jeffrey, Virtanen Suvi M, Hagopian William
Department of Epidemiology, Colorado School of Public Health, University of Colorado Anschutz Medical Campus, Aurora, CO
Health Informatics Institute, Morsani College of Medicine, University of South Florida, Tampa, FL.
Diabetes. 2018 Jan;67(1):146-154. doi: 10.2337/db17-0802. Epub 2017 Oct 23.
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 , and 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 rs7975232 (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 and may have a combined role in IA development in children at increased genetic risk for type 1 diabetes.
我们研究了血浆25-羟维生素D[25(OH)D]浓度与胰岛自身免疫(IA)之间的关联，以及维生素D基因多态性是否会改变25(OH)D对IA风险的影响。我们在美国和欧洲的六个地点对8676名1型糖尿病遗传风险增加的儿童进行了随访。我们将IA定义为在两次或更多次就诊时至少一种自身抗体(GADA、IAA或IA-2A)呈阳性。我们对376例IA病例受试者进行了风险集抽样巢式病例对照研究，每个病例受试者最多有3名对照受试者。在首次IA阳性就诊之前及包括该次就诊在内的所有样本中均测量了25(OH)D浓度。分析了、和中的9种多态性作为25(OH)D的效应修饰因子。在调整HLA-DR-DQ和血统后，儿童期较高的25(OH)D与较低的IA风险相关(5 nmol/L差异的优势比=0.93；95%CI 0.89，0.97)。此外，这种关联被rs7975232修饰(交互作用=0.0072)，根据次要等位基因数量，儿童期25(OH)D升高与IA风险降低相关：0个(1.00；0.93，1.07)、1个(0.92；0.89，0.96)和2个(0.86；0.80，0.92)。维生素D和可能在1型糖尿病遗传风险增加的儿童IA发生中具有联合作用。
