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Type 1 Diabetes 14 percent more likely with 2 Vitamin D Receptor mutations – Oct 2017

Plasma 25-Hydroxyvitamin D Concentration and Risk of Islet Autoimmunity.

Diabetes. 2017 Oct 23. pii: db170802. doi: 10.2337/db17-0802. [Epub ahead of print]


Norris JM1, Lee HS2, Frederiksen B3, Erlund I4, Uusitalo U2, Yang J2, Lernmark Å5, Simell O6, Toppari J6,7, Rewers M8, Ziegler AG9, She JX10, Onengut-Gumuscu S11, Chen WM11, Rich SS11, Sundvall J4, Akolkar B12, Krischer J2, Virtanen SM13, Hagopian W14; TEDDY Study Group.

  • 1 Department of Epidemiology, Colorado School of Public Health, University of Colorado Anschutz Medical Campus, Aurora, CO, USA jill.norris at ucdenver.edu.
  • 2 Health Informatics Institute, Morsani College of Medicine, University of South Florida, Tampa, FL, USA.
  • 3 Department of Epidemiology, Colorado School of Public Health, University of Colorado Anschutz Medical Campus, Aurora, CO, USA.
  • 4 Department of Health, Genomics and Biomarkers Unit, National Institute for Health and Welfare, Helsinki, Finland.
  • 5 Department of Clinical Sciences, Lund University/CRC, Malmö, Sweden.
  • 6 Department of Pediatrics, Turku University Hospital, Turku, Finland.
  • 7 Department of Physiology, Institute of Biomedicine, University of Turku, Turku, Finland.
  • 8 Barbara Davis Center for Childhood Diabetes, University of Colorado Denver, Aurora, CO, USA.
  • 9 Department of Pediatrics, Diabetes Research Institute, Munich, Germany.
  • 10 Center for Biotechnology and Genomic Medicine, Augusta University, Augusta, GA, USA.
  • 11 Center for Public Health Genomics, University of Virginia, Charlottesville, VA, USA.
  • 12 National Institutes of Diabetes and Digestive and Kidney Disorders, National Institutes of Health, Bethesda, MD, USA.
  • 13 National Institute for Health and Welfare, Nutrition Unit, Helsinki; University of Tampere, School of Health Sciences; Center for Child Health Research, University of Tampere and Tampere University Hospital; and The Science Center of Pirkanmaa Hospital District, Tampere, Finland.
  • 14 Pacific Northwest Diabetes Research Institute, Seattle, WA, USA.

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 8676 children at increased genetic risk of type 1 diabetes(T1D) at 6 sites in the US and Europe. We defined IA as positivity for at least one autoantibody (GADA, IAA or IA-2A) on 2 or more visits. We conducted a risk-set sampled nested case-control study of 376 IA cases and up to 3 controls per case. 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(OR): 0.93 for a 5 nmol/L difference; 95% confidence interval(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 (OR:1.00; CI:0.93,1.07),
  • 1 (OR:0.92; CI:0.89,0.96), and
  • 2 (OR:0.86; CI:0.80,0.92).

Vitamin D and VDR may have a combined role in IA development in children at increased genetic risk for T1D.

PMID: 29061729 DOI: 10.2337/db17-0802
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