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

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Torn , C , Liu , X , Hagopian , W , Lernmark , A , Simell , O , Rewers , M , Ziegler , A-G , Schatz , D , Akolkar , B , Onengut-Gumuscu , S , Chen , W-M , Toppari , J , Mykkanen , J , Ilonen , J , Rich , S S , She , J-X , Sharma , A , Steck , A , Krischer , J , TEDDY Study Grp & Knip , M 2016 , ' Complement gene variants in relation to autoantibodies to beta cell specific antigens and type 1 diabetes in the TEDDY Study ' , Scientific Reports , vol. 6 , 27887 . https://doi.org/10.1038/srep27887

Title: Complement gene variants in relation to autoantibodies to beta cell specific antigens and type 1 diabetes in the TEDDY Study
Author: Torn, Carina; Liu, Xiang; Hagopian, William; Lernmark, Ake; Simell, Olli; Rewers, Marian; Ziegler, Anette-G; Schatz, Desmond; Akolkar, Beena; Onengut-Gumuscu, Suna; Chen, Wei-Min; Toppari, Jorma; Mykkanen, Juha; Ilonen, Jorma; Rich, Stephen S.; She, Jin-Xiong; Sharma, Ashok; Steck, Andrea; Krischer, Jeffrey; TEDDY Study Grp; Knip, Mikael
Contributor: University of Helsinki, Clinicum
Date: 2016-06-16
Language: eng
Number of pages: 10
Belongs to series: Scientific Reports
ISSN: 2045-2322
URI: http://hdl.handle.net/10138/174573
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.
Subject: ANTIBODY STANDARDIZATION PROGRAM
SYSTEMIC-LUPUS-ERYTHEMATOSUS
GLUTAMIC-ACID DECARBOXYLASE
GENOME-WIDE ASSOCIATION
MACULAR DEGENERATION
EXTENDED HAPLOTYPES
ISLET ANTIGEN-2
CLASS-I
RISK
HLA
3111 Biomedicine
3121 General medicine, internal medicine and other clinical medicine
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