title: Effect of autoimmunity risk loci on the honeymoon phase in type 1 diabetes.
abstract: OBJECTIVE
  To analyze the correlation between duration and depth of honeymoon phase in patients with type 1 diabetes (T1DM) and autoimmunity risk loci.
  
  
  METHODS
  From a database of 567 individuals with clinical data, we selected 210 patients for whom we had dense genotyping results of single-nucleotide polymorphisms (SNPs) from our previous genome-wide association studies (GWAS) or targeted genotyping data. Using PLINK software, we analyzed the association between time spent in honeymoon phase as our quantitative trait, and 24 known autoimmunity predisposing SNPs.
  
  
  RESULTS
  We found one allele on chromosome 5, rs4613763 mapping to a Prostaglandin Receptor EP4 (PTGER4) to reach statistical significance (P = .0067), in determining a larger proportion of T1DM patients with a detectable honeymoon phase. This polymorphism determines risk for inflammatory bowel disease (IBD) but not T1DM.
  
  
  CONCLUSIONS
  By showing the role of PTGER4 in autoimmune diseases and its effect on inflammatory responses via its interaction with NF-kB, we hypothesize that PTGER4 modulates honeymoon phase in patients with T1DM without influencing the risk of developing T1DM. We hypothesize that this quantitative trait locus promotes inflammatory suppression of beta cells without directly promoting beta-cell destruction. Understanding SNPs that effect function can provide insight in to pathogenesis of T1DM and the mechanism of the honeymoon phase. Because this is a hypothesis-generating study, it needs to be replicated in an additional larger cohort.
authors: Department of Endocrinology, University of British Columbia, Vancouver, Canada.
authors: Mandana
authors: M
authors: Moosavi
authors: Department of Pediatrics, McGill University, Montreal, Canada.
authors: Jade
authors: J
authors: Séguin
authors: Department of Pediatrics, McGill University, Montreal, Canada.
authors: Constantin
authors: C
authors: Polychronakos
mesh_terms: D002648:Child; D003922:Diabetes Mellitus, Type 1 / Q000188:drug therapy* / Q000235:genetics* / Q000276:immunology; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D007328:Insulin / Q000627:therapeutic use*; D012074:Remission Induction
chemical_list: D007004:Hypoglycemic Agents; D007328:Insulin
keywords: diabetes; insulin; polymorphism; quantitative trait