Objective: We studied if vitamin D intake was associated with risk of IA or progression to T1D and whether single nucleotide polymorphisms (SNP) in vitamin D metabolism genes modify the effect of intake on risk.
Methods: We followed 7,520 high risk children from birth until development of IA, defined as persistent GAD65 (GADA), insulin (IAA) and/or IA-2 autoantibodies, and until progression to T1D. Vitamin D intake from foods and supplements was estimated with 3 day food records collected quarterly in the first year and then semi-annually to age 10. We analyzed vitamin D per energy intake in time-dependent Cox proportional hazards models, adjusting for country, sex, T1D family history, HLA, energy, ancestry and seroconversion age (for progression analysis). We tested interactions between intake and 18 SNPs in GC, CYP2R1, CYP24A1, DHCR7 and VDR on risk of IA and progression to T1D using a false discovery rate of <0.05 for significance.
Results: Higher vitamin D intake was associated with increased risk of GADA-first, only in those with 2 minor alleles in a SNP in CYP24A1 (which inactivates vitamin D) (Figure). Higher vitamin D intake at seroconversion was associated with decreased risk of progression from IA to T1D, only in those with no minor alleles in SNPs in GC (vitamin D binding protein gene) and VDR (vitamin D receptor gene).
Conclusion: Vitamin D intake may have differing effects on risk of IA and T1D, depending on variants in vitamin D genes.
J.M. Norris: None. J.L. Clasen: None. X. Liu: None. U. Uusitalo: None. C. Andrén Aronsson: None. S. Hummel: None. J. Yang: None. M. Rewers: Advisory Panel; Sanofi. Other Relationship; Sanofi. Consultant; Janssen Pharmaceuticals, Inc. Research Support; Juvenile Diabetes Research Foundation (JDRF). Consultant; Provention Bio, Inc. Research Support; Hemsley Charitable Trust, National Institute of Diabetes and Digestive and Kidney Diseases. R. McIndoe: None. W. Hagopian: Research Support; Janssen Pharmaceuticals, Inc., Provention Bio, Inc. Consultant; Sanofi-Aventis U.S., Randox R & D. A. Ziegler: None. Å. Lernmark: Advisory Panel; DiaMyd Medical AB, Stockholm, Sweden. J. Toppari: None. S.S. Rich: None. S. Onengut-Gumuscu: None. H.M. Parikh: None. I.A.M. Erlund: None. B. Akolkar: None. J. Krischer: None. S. Virtanen: None.
NIH NIDDK (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, UC4 DK112243, UC4 DK117483, U01 DK124166, U01 DK128847, and Contract No. HHSN267200700014C)
