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Sci Rep. 2016 Jun 16;6:27887. doi: 10.1038/srep27887.

Complement gene variants in relation to autoantibodies to beta cell specific antigens and type 1 diabetes in the TEDDY Study.

Collaborators (161)

Abbondondolo M, Adams J, Adamsson A, Agardh D, Anderson SW, Aronsson CA, Ask M, Austin-Gonzalez S, Ayres S, Baethke S, Bautista K, Baxter J, Becker D, Bedoy R, Bennet R, Johnson SB, Beyerlein A, Bonifacio E, Bourcier K, Bremer J, Briese T, Brown R, Burkhardt B, Butterworth M, Carlsson UM, Cilio C, Clasen J, Crouch CC, Cuthbertson D, Daftary A, Dalmagro-Elias M, Dunson K, Eberhard C, Larsson HE, Ericsson-Hallström E, Felipe-Morales D, Fiske S, Foghis G, Foterek K, Fransiscus M, Fransson L, Frohnert BI, Garcia D, Gard T, Gardiner M, Garmeson J, Gerardsson J, Gesualdo P, Gowda V, Haller M, Hansen M, Hansson G, Harmby C, Hervey R, Heyman K, Hoffman M, Hopkins D, Hummel M, Hummel S, Hyberg S, Hyöty H, Johansen F, Johnson C, Jokipuu S, Jonasdottir B, Kallio T, Karban R, Kersting M, Killian M, Klein B, Knip M, Knopff A, Koivu A, Koletzko S, Koreasalo M, Kurppa K, Kähönen M, Lee HS, Forss SL, Liu E, Liu S, Lundgren M, Lynch K, Lyons R, Lönnrot M, Malloy J, Markan M, McCarthy C, McIndoe R, McLeod W, Melin J, Mestan Z, Meulemans S, Meyer A, Mulenga D, Multasuo K, Månsson-Martinez M, Mäntimäki E, Niinien T, Norris J, Nyblom M, Peplow C, Laras FP, Rahmati K, Rajala P, Ramelius A, Rautanen J, Riikonen A, Robinson R, Romo M, Rosenquist A, Roth R, Salami F, Samper-Imaz A, Scott E, Shaffer C, Sibthorpe S, Silvis K, Simell S, Simell V, Sjöberg M, Sjöberg B, Skidmore J, Smith L, Smith S, Stabbert J, Steed L, Stenius A, Stock J, Strauss E, Sulman N, Swartling U, Särmä M, Tamura R, Tarr A, Amboh ET, Thomas J, Triplett E, Trulsson E, Uland M, Uusitalo U, Vainionpää S, Wallin A, Varionen E, Warncke K, Waugh K, Vehik K, Veijola R, Vijayakandipan P, Williams J, Willis J, Wimar Å, Winkler C, Virtanen SM, Wood K, Wright H, Vähä-Mäkilä M, Yang J, Yates C, Åberg S, Åkerlund M.

Author information

1
Department of Clinical Sciences, Lund University/CRC, Malmö, Sweden.
2
Health Informatics Institute, Morsani College of Medicine, University of South Florida, Tampa, FL, USA.
3
Pacific Northwest Diabetes Research Institute, Seattle, WA, USA.
4
Department of Pediatrics, Turku University Hospital, Turku, Finland.
5
Barbara Davis Center for Childhood Diabetes, University of Colorado, Aurora, CO, USA.
6
Institute of Diabetes Research, Helmholtz Zentrum, München, and Klinikum rechts der Isar, Technische Universität München, and Forschergruppe Diabetes e. V., Neuherberg, Germany.
7
Department of Pediatrics, University of Florida, Gainesville, FL, USA.
8
National Institutes of Diabetes &Digestive &Kidney Disorders, Bethesda, MD, USA.
9
Center for Public Health Genomic, University of Virginia, Charlottesville, VA, USA.
10
Departments of Physiology and Pediatrics, University of Turku, Turku, Finland.
11
Center for Biotechnology and Genomic Medicine, Medical College of Georgia, Augusta University, Augusta, GA, USA.

Abstract

A total of 15 SNPs within complement genes and present on the ImmunoChip were analyzed in The Environmental Determinants of Diabetes in the Young (TEDDY) study. A total of 5474 subjects were followed from three months of age until islet autoimmunity (IA: n = 413) and the subsequent onset of type 1 diabetes (n = 115) for a median of 73 months (IQR 54-91). Three SNPs within ITGAM were nominally associated (p < 0.05) with IA: rs1143678 [Hazard ratio; HR 0.80; 95% CI 0.66-0.98; p = 0.032], rs1143683 [HR 0.80; 95% CI 0.65-0.98; p = 0.030] and rs4597342 [HR 1.16; 95% CI 1.01-1.32; p = 0.041]. When type 1 diabetes was the outcome, in DR3/4 subjects, there was nominal significance for two SNPs: rs17615 in CD21 [HR 1.52; 95% CI 1.05-2.20; p = 0.025] and rs4844573 in C4BPA [HR 0.63; 95% CI 0.43-0.92; p = 0.017]. Among DR4/4 subjects, rs2230199 in C3 was significantly associated [HR 3.20; 95% CI 1.75-5.85; p = 0.0002, uncorrected] a significance that withstood Bonferroni correction since it was less than 0.000833 (0.05/60) in the HLA-specific analyses. SNPs within the complement genes may contribute to IA, the first step to type 1 diabetes, with at least one SNP in C3 significantly associated with clinically diagnosed type 1 diabetes.

PMID:
27306948
PMCID:
PMC4910045
DOI:
10.1038/srep27887
[Indexed for MEDLINE]
Free PMC Article

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