Clinical and genetic characteristics of autoimmune polyglandular syndrome type 3 variant in the Japanese population

J Clin Endocrinol Metab. 2012 Jun;97(6):E1043-50. doi: 10.1210/jc.2011-3109. Epub 2012 Mar 30.


Objective: Type 1 diabetes (T1D) is commonly associated with autoimmune thyroid disease (AITD), and the occurrence of both T1D and AITD in a patient is defined as autoimmune polyglandular syndrome type 3 variant (APS3v). We aimed to clarify the differences in the clinical and genetic characteristics of APS3v patients and T1D patients without AITD [T1D/AITD(-)] in the Japanese population.

Design/patients: Our subjects were 54 APS3v patients and 143 T1D/AITD(-) patients who were consecutively diagnosed at Nagasaki University Hospital from 1983 to the present.

Results: A remarkable female predominance, a slow and older age onset of T1D, and a higher prevalence of glutamic acid decarboxylase autoantibodies were observed in APS3v patients compared to T1D/AITD(-) patients. The older onset age of T1D in APS3v patients was associated with a higher proportion of slow-onset T1D. Among the two major susceptible human leukocyte antigen (HLA) class II haplotypes in Japanese T1D, DRB1*0405-DQB1*0401, but not DRB1*0901-DQB1*0303, was associated with APS3v patients. Furthermore, DRB1*0803-DQB1*0601 was not protective in patients with APS3v. The frequencies of the GG genotype in +49G>A and +6230G>A polymorphism in the CTLA4 gene were significantly higher in T1D/AITD(-) patients, but not in APS3v patients, compared to control subjects.

Conclusions: In conclusion, we found notable differences in the clinical and genetic characteristics of APS3v patients and T1D/AITD(-) patients in the Japanese population, and the differences in the clinical characteristics between the two groups may reflect distinct genetic backgrounds including the HLA DRB1-DQB1 haplotypes and CTLA4 gene polymorphisms.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Age of Onset
  • Asian People / genetics*
  • Asian People / statistics & numerical data*
  • Autoantibodies / blood
  • Autoantibodies / immunology
  • Child
  • Child, Preschool
  • Diabetes Mellitus, Type 1 / ethnology*
  • Diabetes Mellitus, Type 1 / genetics*
  • Diabetes Mellitus, Type 1 / immunology
  • Female
  • HLA-DQ beta-Chains / genetics
  • HLA-DRB1 Chains / genetics
  • Haplotypes
  • Humans
  • Islets of Langerhans / immunology
  • Japan / epidemiology
  • Male
  • Middle Aged
  • Polyendocrinopathies, Autoimmune / ethnology*
  • Polyendocrinopathies, Autoimmune / genetics*
  • Polyendocrinopathies, Autoimmune / immunology
  • Prevalence
  • Seroepidemiologic Studies
  • Sex Distribution
  • Thyroiditis, Autoimmune / ethnology
  • Thyroiditis, Autoimmune / genetics
  • Thyroiditis, Autoimmune / immunology
  • Young Adult


  • Autoantibodies
  • HLA-DQ beta-Chains
  • HLA-DQB1 antigen
  • HLA-DRB1 Chains