title: NeuroD/beta2 gene G-->A polymorphism may affect onset pattern of type 1 diabetes in Japanese.
abstract: OBJECTIVE
  The majority of type 1 diabetes is considered to be autoimmune with, for the most part, abrupt development. However, type 1 diabetes with slow onset, or the so-called slowly progressive type 1 diabetes or latent autoimmune diabetes in adults, has been recently recognized and is considered to be autoimmune-related. Although some investigators tried to explain the difference in onset pattern by the genetic background, including HLA type, it has not been established thus far. We hypothesized that the difference in onset pattern may relate to regeneration or differentiation of pancreatic beta-cells, and we therefore focused on the NeuroD/BETA2 gene, which encodes a transcription factor for the insulin gene and beta-cell differentiation.
  
  
  METHODS
  We examined the NeuroD/BETA2 gene polymorphism in 105 Japanese type 1 diabetic patients and in 122 nondiabetic Japanese subjects in a case-control study, and we stratified the patients according to their onset pattern and islet-associated autoantibody positivity.
  
  
  RESULTS
  Regardless of the existence of islet-associated autoantibody, we found a significant difference in A allele frequency between type 1 diabetic patients with acute-onset type and control subjects. However, no difference was found between type 1 slow-onset diabetic patients and control subjects.
  
  
  CONCLUSIONS
  These results support our hypothesis that NeuroD/BETA2 may affect the ability of regeneration of beta-cells, leading to a difference in the onset pattern and clinical course of type 1 diabetes.
authors.affiliation: Department of Internal Medicine, Keio University School of Medicine, Tokyo, Japan. asmd@med.keio.ac.jp
authors.forename: S
authors.initials: S
authors.lastname: Yamada
authors.forename: Y
authors.initials: Y
authors.lastname: Motohashi
authors.forename: T
authors.initials: T
authors.lastname: Yanagawa
authors.forename: T
authors.initials: T
authors.lastname: Maruyama
authors.forename: A
authors.initials: A
authors.lastname: Kasuga
authors.forename: H
authors.initials: H
authors.lastname: Hirose
authors.forename: K
authors.initials: K
authors.lastname: Matsubara
authors.forename: A
authors.initials: A
authors.lastname: Shimada
authors.forename: T
authors.initials: T
authors.lastname: Saruta
mesh_terms: D000293:Adolescent; D000328:Adult; D017668:Age of Onset; D000368:Aged; D044466:Asian People; D001323:Autoantibodies / Q000097:blood; D051792:Basic Helix-Loop-Helix Proteins; D016022:Case-Control Studies; D002454:Cell Differentiation; D002648:Child; D002675:Child, Preschool; D004268:DNA-Binding Proteins / Q000235:genetics*; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics* / Q000276:immunology / Q000503:physiopathology*; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D007515:Islets of Langerhans / Q000166:cytology / Q000276:immunology; D007564:Japan; D008875:Middle Aged; D017354:Point Mutation; D011110:Polymorphism, Genetic; D012016:Reference Values; D015534:Trans-Activators / Q000235:genetics*; D014157:Transcription Factors / Q000235:genetics
chemical_list: D001323:Autoantibodies; D051792:Basic Helix-Loop-Helix Proteins; D004268:DNA-Binding Proteins; D015534:Trans-Activators; D014157:Transcription Factors; C093970:NEUROD1 protein, human