title: Clinical and genetic characteristics of autoimmune polyglandular syndrome type 3 variant in the Japanese population.
abstract: 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.
  
  
  METHODS
  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.
authors.affiliation: Department of Metabolism/Diabetes and Clinical Nutrition, Nagasaki University Hospital, 1-7-1 Sakamoto, Nagasaki 852-8501, Japan.
authors.forename: Ichiro
authors.initials: I
authors.lastname: Horie
authors.forename: Eiji
authors.initials: E
authors.lastname: Kawasaki
authors.forename: Takao
authors.initials: T
authors.lastname: Ando
authors.forename: Hironaga
authors.initials: H
authors.lastname: Kuwahara
authors.forename: Norio
authors.initials: N
authors.lastname: Abiru
authors.forename: Toshiro
authors.initials: T
authors.lastname: Usa
authors.forename: Hironori
authors.initials: H
authors.lastname: Yamasaki
authors.forename: Eri
authors.initials: E
authors.lastname: Ejima
authors.forename: Atsushi
authors.initials: A
authors.lastname: Kawakami
mesh_terms: D000293:Adolescent; D000328:Adult; D017668:Age of Onset; D044466:Asian People / Q000235:genetics* / Q000706:statistics & numerical data*; D001323:Autoantibodies / Q000097:blood / Q000276:immunology; D002648:Child; D002675:Child, Preschool; D003922:Diabetes Mellitus, Type 1 / Q000208:ethnology* / Q000235:genetics* / Q000276:immunology; D005260:Female; D059866:HLA-DQ beta-Chains / Q000235:genetics; D059811:HLA-DRB1 Chains / Q000235:genetics; D006239:Haplotypes; D006801:Humans; D007515:Islets of Langerhans / Q000276:immunology; D007564:Japan / Q000453:epidemiology; D008297:Male; D008875:Middle Aged; D016884:Polyendocrinopathies, Autoimmune / Q000208:ethnology* / Q000235:genetics* / Q000276:immunology; D015995:Prevalence; D016036:Seroepidemiologic Studies; D017678:Sex Distribution; D013967:Thyroiditis, Autoimmune / Q000208:ethnology / Q000235:genetics / Q000276:immunology; D055815:Young Adult
chemical_list: D001323:Autoantibodies; D059866:HLA-DQ beta-Chains; C069051:HLA-DQB1 antigen; D059811:HLA-DRB1 Chains