Genetic and environmental interactions modify the risk of diabetes-related autoimmunity by 6 years of age: The teddy study

Research output: Contribution to journalArticle

Abstract

OBJECTIVE We tested the associations between genetic background and selected environmental exposures with respect to islet autoantibodies and type 1 diabetes. RESEARCH DESIGN AND METHODS Infants with HLA-DR high-risk genotypes were prospectively followed for diabetesrelated autoantibodies. Single nucleotide polymorphisms (SNPs) came from the Illumina ImmunoChip and environmental exposure data were by parental report. Children were followed to age 6 years. RESULTS Insulin autoantibodies occurred earlier than GAD antibody (GADA) and then declined, while GADA incidence rose and remained constant (significant in HLA-DR4 but not in the DR3/3 children). The presence of SNPs rs2476601 (PTPN22) and rs2292239 (ERBB3) demonstrated increased risk of both autoantibodies to insulin (IAA) only and GADA only. SNP rs689 (INS) was protective of IAA only, but not of GADA only. The rs3757247 (BACH2) SNP demonstrated increased risk of GADA only. Male sex, father or sibling as the diabetic proband, introduction of probiotics under 28 days of age, and weight at age 12 monthswere associated with IAA only, but only father as the diabetic proband and weight at age 12 months were associated with GADA only. Mother as the diabetic proband was not a significant risk factor. CONCLUSIONS These results show clear differences in the initiation of autoimmunity according to genetic factors and environmental exposures that give rise to IAAorGADA as the first appearing indication of autoimmunity.

Details

Authors
  • Jeffrey P. Krischer
  • Kristian F Lynch
  • Ake Lernmark
  • William A Hagopian
  • Marian J. Rewers
  • Jin-Xiong She
  • Jorma Toppari
  • Anette G. Ziegler
  • Beena Akolkar
Organisations
External organisations
  • Pacific Northwest Diabetes Research Institute
  • University of Colorado
  • Augusta University
  • Turku University Hospital
  • University of Turku
  • Helmholtz Zentrum München
  • Klinikum rechts der Isar
  • National Institute of Diabetes and Digestive and Kidney Diseases
  • University of South Florida
Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Endocrinology and Diabetes

Keywords

  • Diabetes , TEDDY study, genetic interactions, enviromental interactions
Original languageEnglish
Pages (from-to)1194-1202
Number of pages9
JournalDiabetes Care
Volume40
Issue number9
Publication statusPublished - 2017 Sep 1
Publication categoryResearch
Peer-reviewedYes