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.

RESEARCH DESIGN AND 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: Ezio Bonifacio, Katharina Warncke, Christiane Winkler, Maike Wallner, Anette-G Ziegler
• Journal: Diabetes (Diabetes) Vol. 60 Issue 12 Pg. 3300-6 (Dec 2011) ISSN: 1939-327X [Electronic] United States
• PMID: 22110093 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Autoantibodies
• Interleukin-2 Receptor alpha Subunit
• Interferons
• PTPN22 protein, human
• Protein Tyrosine Phosphatase, Non-Receptor Type 22
• IFIH1 protein, human
• DNA Helicases
• DEAD-box RNA Helicases
• Interferon-Induced Helicase, IFIH1

Topics

• Autoantibodies (immunology)
• Cesarean Section (adverse effects)
• DEAD-box RNA Helicases (genetics)
• DNA Helicases (genetics)
• Diabetes Mellitus, Type 1 (epidemiology, etiology, genetics, immunology)
• Female
• Humans
• Infant, Newborn
• Interferon-Induced Helicase, IFIH1
• Interferons
• Interleukin-2 Receptor alpha Subunit (genetics)
• Polymorphism, Genetic (genetics)
• Pregnancy
• Protein Tyrosine Phosphatase, Non-Receptor Type 22 (genetics)
• Risk Factors