The association of Ala45Thr polymorphism in NeuroD with child-onset Type 1a diabetes in Japanese

Diabetes Res Clin Pract. 2002 Jan;55(1):11-7. doi: 10.1016/s0168-8227(01)00242-x.


Recently Iwata et al. reported that the polymorphism in NeuroD exon 2(Ala45Thr) was associated with adult-onset Type 1 diabetes in Japanese. Furthermore, the mutations in the NeuroD as a regulator of insulin transcription have been reported to result in Type 2 diabetes. We, therefore, aimed to clarify the role of this Ala45Thr polymorphism in the susceptibility to Type 1a, immune-mediated, diabetes of child-onset Japanese patients. Eighty patients with child-onset Type 1 diabetes were examined along with 121 non-diabetic subjects as the controls. The polymorphism in Ala45Thr was defined using the PCR-RFLP method. The GAD Ab, IA-2 Ab, HLA-DRB1 genotypes and residual beta-cell function at 3 years from onset were evaluated in relation to the difference in this polymorphism. The frequency of the Ala45Thr heterozygotes was significantly higher in the Type 1 diabetic patients than in the controls (21.3 versus 9.9%, P=0.0252). The frequency of loss of beta-cell function was higher in heterozygotes patients than in wild type homozygotes patients (P=0.0112). Type 1 diabetic patients with DRB1*0901 allele showed a significantly higher frequency, 27.9%, of the Ala45Thr variant than the controls (P=0.0041). In conclusion, the Ala45Thr polymorphism contributes to the risk of development of, and to the early deterioration of beta-cell function, in Type 1a diabetes among the Japanese population.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Age of Onset
  • Alanine
  • Alleles
  • Asian Continental Ancestry Group
  • Basic Helix-Loop-Helix Transcription Factors
  • Child
  • Diabetes Mellitus, Type 1 / genetics*
  • Genetic Carrier Screening
  • Genetic Predisposition to Disease
  • Genetic Variation
  • HLA-DR Antigens / genetics
  • HLA-DRB1 Chains
  • Helix-Loop-Helix Motifs
  • Homozygote
  • Humans
  • Japan
  • Nerve Tissue Proteins / genetics*
  • Polymerase Chain Reaction
  • Polymorphism, Genetic*
  • Polymorphism, Restriction Fragment Length
  • Reference Values
  • Threonine
  • Time Factors


  • Basic Helix-Loop-Helix Transcription Factors
  • HLA-DR Antigens
  • HLA-DRB1 Chains
  • Nerve Tissue Proteins
  • NeuroD protein
  • Threonine
  • Alanine