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

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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.

Details

Authors
  • Carina Törn
  • Xiang Liu
  • William Hagopian
  • Olli Simell
  • Marian Rewers
  • Anette G. Ziegler
  • Desmond Schatz
  • Beena Akolkar
  • Suna Onengut-Gumuscu
  • Wei Min Chen
  • Jorma Toppari
  • Juha Mykkänen
  • Jorma Ilonen
  • Stephen S. Rich
  • Jin Xiong She
  • Ashok Sharma
  • Andrea Steck
  • Jeffrey Krischer
  • Maria Ask
  • Rasmus Bennet
  • Jenny Bremer
  • Ulla-Marie Carlsson
  • Lina Fransson
  • Thomas Gard
  • Joanna Gerardsson
  • Monica Hansen
  • Gertie Hansson
  • Cecilia Harmby
  • Suzanne Hyberg-Karlsson
  • Fredrik Johansen
  • Sigrid Lenrick Forss
  • Maria Markan
  • Zeliha Mestan
  • Maria Månsson Martinez
  • Kobra Rahmati
  • Anita Ramelius
  • Anna Rosenquist
  • Sara Sibthorpe
  • Ulrica Swartling
  • Evelyn Tekum Amboh
  • Anne Wallin
  • Åsa Wimar
  • Sofie Åberg
Organisations
External organisations
  • Turku University Hospital
  • University of Turku
  • University of South Florida
  • Pacific Northwest Diabetes Research Institute
  • University of Colorado
  • Technical University of Munich
  • University of Florida
  • National Institute of Diabetes and Digestive and Kidney Diseases
  • University of Virginia
  • Augusta University
Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Medical Genetics
  • Endocrinology and Diabetes
Original languageEnglish
Article number27887
JournalScientific Reports
Volume6
Publication statusPublished - 2016 Jun 16
Publication categoryResearch
Peer-reviewedYes