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Cesarean section and interferon-induced helicase gene polymorphisms combine to increase childhood type 1 diabetes risk.
MedLine Citation:
PMID:  22110093     Owner:  NLM     Status:  In-Data-Review    
Abstract/OtherAbstract:
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
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Diabetes     Volume:  60     ISSN:  1939-327X     ISO Abbreviation:  Diabetes     Publication Date:  2011 Dec 
Date Detail:
Created Date:  2011-11-23     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0372763     Medline TA:  Diabetes     Country:  United States    
Other Details:
Languages:  eng     Pagination:  3300-6     Citation Subset:  AIM; IM    
Affiliation:
Corresponding author: Anette-G. Ziegler, anette-g.ziegler@helmholtz-muenchen.de.
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