title: Cesarean section and interferon-induced helicase gene polymorphisms combine to increase childhood type 1 diabetes risk.
abstract: OBJECTIVE
  The incidence of type 1 diabetes is increasing. Delivery by cesarean section is also more prevalent, and it is suggested that cesarean section is associated with type 1 diabetes risk. We examine associations between cesarean delivery, islet autoimmunity and type 1 diabetes, and genes involved in type 1 diabetes susceptibility.
  
  
  METHODS
  Cesarean section was examined as a risk factor in 1,650 children born to a parent with type 1 diabetes and followed from birth for the development of islet autoantibodies and type 1 diabetes.
  
  
  RESULTS
  Children delivered by cesarean section (n = 495) had more than twofold higher risk for type 1 diabetes than children born by vaginal delivery (hazard ratio [HR] 2.5; 95% CI 1.4-4.3; P = 0.001). Cesarean section did not increase the risk for islet autoantibodies (P = 0.6) but was associated with a faster progression to diabetes after the appearance of autoimmunity (P = 0.015). Cesarean section-associated risk was independent of potential confounder variables (adjusted HR 2.7;1.5-5.0; P = 0.001) and observed in children with and without high-risk HLA genotypes. Interestingly, cesarean section appeared to interact with immune response genes, including CD25 and in particular the interferon-induced helicase 1 gene, where increased risk for type 1 diabetes was only seen in children who were delivered by cesarean section and had type 1 diabetes-susceptible IFIH1 genotypes (12-year risk, 9.1 vs. <3% for all other combinations; P < 0.0001).
  
  
  CONCLUSIONS
  These findings suggest that type 1 diabetes risk modification by cesarean section may be linked to viral responses in the preclinical autoantibody-positive disease phase.
authors: Center for Regenerative Therapies, Dresden University of Technology, Dresden, Germany.
authors: Ezio
authors: E
authors: Bonifacio
authors: Katharina
authors: K
authors: Warncke
authors: Christiane
authors: C
authors: Winkler
authors: Maike
authors: M
authors: Wallner
authors: Anette-G
authors: AG
authors: Ziegler
mesh_terms: D001323:Autoantibodies / Q000276:immunology; D002585:Cesarean Section / Q000009:adverse effects*; D053487:DEAD-box RNA Helicases / Q000235:genetics; D004265:DNA Helicases / Q000235:genetics*; D003922:Diabetes Mellitus, Type 1 / Q000453:epidemiology* / Q000209:etiology / Q000235:genetics* / Q000276:immunology; D005260:Female; D006801:Humans; D007231:Infant, Newborn; D000072640:Interferon-Induced Helicase, IFIH1; D007372:Interferons; D053645:Interleukin-2 Receptor alpha Subunit / Q000235:genetics; D011110:Polymorphism, Genetic / Q000235:genetics*; D011247:Pregnancy; D054596:Protein Tyrosine Phosphatase, Non-Receptor Type 22 / Q000235:genetics; D012307:Risk Factors
chemical_list: D001323:Autoantibodies; D053645:Interleukin-2 Receptor alpha Subunit; D007372:Interferons; C516765:PTPN22 protein, human; D054596:Protein Tyrosine Phosphatase, Non-Receptor Type 22; C452815:IFIH1 protein, human; D004265:DNA Helicases; D053487:DEAD-box RNA Helicases; D000072640:Interferon-Induced Helicase, IFIH1