A1 Refereed original research article in a scientific journal
Complement gene variants in relation to autoantibodies to beta cell specific antigens and type 1 diabetes in the TEDDY Study
Authors: Torn C, Liu X, Hagopian W, Lernmark A, Simell O, Rewers M, Ziegler AG, Schatz D, Akolkar B, Onengut-Gumuscu S, Chen WM, Toppari J, Mykkanen J, Ilonen J, Rich SS, She JX, Sharma A, Steck A, Krischer J & The TEDDY Study Group
Publisher: NATURE PUBLISHING GROUP
Publishing place: London
Publication year: 2016
Journal: Scientific Reports
Journal name in source: SCIENTIFIC REPORTS
Journal acronym: SCI REP-UK
Article number: ARTN 27887
Volume: 6
First page : 1
Last page: 10
Number of pages: 10
ISSN: 2045-2322
eISSN: 2045-2322
DOI: https://doi.org/10.1038/srep27887
Web address : http://www.nature.com/articles/srep27887
Self-archived copy’s web address: https://www.researchgate.net/publication/304027464_Complement_gene_variants_in_relation_to_autoantibodies_to_beta_cell_specific_antigens_and_type_1_diabetes_in_the_TEDDY_Study
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.
Downloadable publication This is an electronic reprint of the original article. |  |
