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.
Department of Clinical Sciences, Lund University/CRC, Malmö, Sweden.
Carina
C
Törn
Health Informatics Institute, Morsani College of Medicine, University of South Florida, Tampa, FL, USA.
Xiang
X
Liu
Pacific Northwest Diabetes Research Institute, Seattle, WA, USA.
William
W
Hagopian
Department of Clinical Sciences, Lund University/CRC, Malmö, Sweden.
Åke
Å
Lernmark
Department of Pediatrics, Turku University Hospital, Turku, Finland.
Olli
O
Simell
Barbara Davis Center for Childhood Diabetes, University of Colorado, Aurora, CO, USA.
Marian
M
Rewers
Institute of Diabetes Research, Helmholtz Zentrum, München, and Klinikum rechts der Isar, Technische Universität München, and Forschergruppe Diabetes e. V., Neuherberg, Germany.
Anette-G
AG
Ziegler
Department of Pediatrics, University of Florida, Gainesville, FL, USA.
Desmond
D
Schatz
National Institutes of Diabetes &Digestive &Kidney Disorders, Bethesda, MD, USA.
Beena
B
Akolkar
Center for Public Health Genomic, University of Virginia, Charlottesville, VA, USA.
Suna
S
Onengut-Gumuscu
Center for Public Health Genomic, University of Virginia, Charlottesville, VA, USA.
Wei-Min
WM
Chen
Department of Pediatrics, Turku University Hospital, Turku, Finland.|Departments of Physiology and Pediatrics, University of Turku, Turku, Finland.
Jorma
J
Toppari
Department of Pediatrics, Turku University Hospital, Turku, Finland.|Departments of Physiology and Pediatrics, University of Turku, Turku, Finland.
Juha
J
Mykkänen
Departments of Physiology and Pediatrics, University of Turku, Turku, Finland.
Jorma
J
Ilonen
Center for Public Health Genomic, University of Virginia, Charlottesville, VA, USA.
Stephen S
SS
Rich
Center for Biotechnology and Genomic Medicine, Medical College of Georgia, Augusta University, Augusta, GA, USA.
Jin-Xiong
JX
She
Center for Biotechnology and Genomic Medicine, Medical College of Georgia, Augusta University, Augusta, GA, USA.
Ashok
A
Sharma
Barbara Davis Center for Childhood Diabetes, University of Colorado, Aurora, CO, USA.
Andrea
A
Steck
Health Informatics Institute, Morsani College of Medicine, University of South Florida, Tampa, FL, USA.
Jeffrey
J
Krischer
D001323:Autoantibodies; D002675:Child, Preschool; D003176:Complement C3 / Q000235:genetics* / Q000276:immunology; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics* / Q000276:immunology; D005260:Female; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D050417:Insulin-Secreting Cells; D008297:Male; D020641:Polymorphism, Single Nucleotide
D001323:Autoantibodies; D003176:Complement C3