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Diabetes. 2018 Jan;67(1):146-154. doi: 10.2337/db17-0802. Epub 2017 Oct 23.

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

Collaborators (215)

Rewers M, Bautista K, Baxter J, Bedoy R, Felipe-Morales D, Driscoll K, Frohnert BI, Gesualdo P, Hoffman M, Karban R, Liu E, Norris J, Samper-Imaz A, Steck A, Waugh K, Wright H, Toppari J, Simell OG, Adamsson A, Ahonen S, Hyöty H, Ilonen J, Jokipuu S, Kallio T, Karlsson L, Kähönen M, Knip M, Kovanen L, Koreasalo M, Kurppa K, Latva-Aho T, Lönnrot M, Mäntymäki E, Multasuo K, Mykkänen J, Niininen T, Niinistö S, Nyblom M, Rajala P, Rautanen J, Riikonen A, Riikonen M, Rouhiainen J, Romo M, Simell T, Simell V, Sjöberg M, Stenius A, Leppänen M, Vainionpää S, Varjonen E, Veijola R, Virtanen SM, Vähä-Mäkilä M, Åkerlund M, Lindfors K, She JX, Schatz D, Hopkins D, Steed L, Thomas J, Adams J, Silvis K, Haller M, Gardiner M, McIndoe R, Sharma A, Williams J, Young G, Anderson SW, Jacobsen L, Ziegler AG, Beyerlein A, Bonifacio E, Hummel M, Hummel S, Foterek K, Janz N, Kersting M, Knopff A, Koletzko S, Peplow C, Roth R, Scholz M, Stock J, Warncke K, Wendel L, Winkler C, Lernmark Å, Agardh D, Aronsson CA, Ask M, Bremer J, Carlsson UM, Cilio C, Ericson-Hallström E, Fransson L, Gard T, Gerardsson J, Bennet R, Hansen M, Hansson G, Hyberg S, Johansen F, Jonsdottir B, Larsson HE, Lindström M, Lundgren M, Månsson-Martinez M, Markan M, Melin J, Mestan Z, Ottosson K, Rahmati K, Ramelius A, Salami F, Sibthorpe S, Sjöberg B, Swartling U, Amboh ET, Törn C, Wallin A, Wimar Å, Åberg S, Hagopian WA, Killian M, Crouch CC, Skidmore J, Carson J, Dalzell M, Dunson K, Hervey R, Johnson C, Lyons R, Meyer A, Mulenga D, Tarr A, Uland M, Willis J, Becker D, Franciscus M, Dalmagro-Elias Smith M, Daftary A, Klein MB, Yates C, Krischer JP, Abbondondolo M, Austin-Gonzalez S, Avendano M, Baethke S, Brown R, Burkhardt B, Butterworth M, Clasen J, Cuthbertson D, Eberhard C, Fiske S, Garcia D, Garmeson J, Gowda V, Heyman K, Laras FP, Lee HS, Liu S, Liu X, Lynch K, Malloy J, McCarthy C, Meulemans S, Parikh H, Shaffer C, Smith L, Smith S, Sulman N, Tamura R, Uusitalo U, Vehik K, Vijayakandipan P, Wood K, Yang J, Akolkar B, Bourcier K, Briese T, Johnson SB, Triplett E, Yu L, Miao D, Bingley P, Williams A, Chandler K, Rokni S, Williams C, Wyatt R, George G, Grace S, Erlund I, Salminen I, Sundvall J, Leiviskä J, Kangas N, Arohonka P, Erlich H, Mack SJ, Fear AL, Ke S, Mulholland N, Rich SS, Chen WM, Onengut-Gumuscu S, Farber E, Pickin RR, Davis J, Gallo D, Bonnie J, Campolieto P.

Author information

1
Department of Epidemiology, Colorado School of Public Health, University of Colorado Anschutz Medical Campus, Aurora, CO jill.norris@ucdenver.edu.
2
Health Informatics Institute, Morsani College of Medicine, University of South Florida, Tampa, FL.
3
Department of Epidemiology, Colorado School of Public Health, University of Colorado Anschutz Medical Campus, Aurora, CO.
4
Genomics and Biomarkers Unit, Department of Health, National Institute for Health and Welfare, Helsinki, Finland.
5
Department of Clinical Sciences, Lund University Clinical Research Centre, 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 Anschutz Medical Campus, Aurora, CO.
9
Department of Pediatrics, Diabetes Research Institute, Munich, Germany.
10
Center for Biotechnology and Genomic Medicine, Augusta University, Augusta, GA.
11
Center for Public Health Genomics, University of Virginia, Charlottesville, VA.
12
National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD.
13
Nutrition Unit, National Institute for Health and Welfare, Helsinki, Finland; School of Health Sciences, University of Tampere; 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.

Abstract

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 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.

PMID:
29061729
PMCID:
PMC5741144
DOI:
10.2337/db17-0802
[Indexed for MEDLINE]
Free PMC Article

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