title: Susceptibility alleles and haplotypes of human leukocyte antigen DRB1, DQA1, and DQB1 in autoimmune polyglandular syndrome type III in Japanese population.
abstract: BACKGROUND
  It has been reported that HLA class II haplotypes DRB1*0405-DQA1*0303-DQB1*0401 and DRB1*0901-DQA1*0302-DQB1*0303 are major susceptibility haplotypes for type 1 diabetes mellitus (DM) in Japanese population. However, little has been reported on the susceptibility HLA class II haplotypes in Japanese patients with autoimmune polyglandular syndrome type II and type III (APS III).
  
  
  METHODS
  HLA class II haplotypes of DRB1-DQA1-DQB1 in 31 patients with APS III, 14 patients with Hashimoto's thyroiditis alone, and 15 patients with Graves' disease alone were examined in Japanese population. APS III patients were divided into three groups (A, B, and C) depending on the combination of autoimmune endocrine diseases.
  
  
  RESULTS
  In 13 APS III patients with both Hashimoto's thyroiditis and type 1 DM (group A), the haplotype frequencies of the HLA DRB1*0802-DQA1*0401-DQB1*0402 and DRB1*0901-DQA1*0302-DQB1*0303 were significantly higher than in the controls. In patients with Hashimoto's thyroiditis alone, the haplotype frequency of DRB1*0901-DQA1*0302-DQB1*0303 was significantly higher than in controls, whereas the frequency of DRB1*0802-DQA1*0401-DQB1*0402 did not differ significantly from those in the controls. In 11 APS III patients with both Graves' disease and type 1 DM (group B), the haplotype frequencies of HLA DRB1*0405-DQA1*0303-DQB1*0401 and DRB1*0802-DQA1*0301-DQB1*0302 were significantly higher than in controls. In patients with Graves' disease alone, the haplotype frequency of DRB1*0803-DQA1*0103-DQB1*0601 were significantly higher than those in controls, suggesting that the susceptibility haplotypes for group B APS III differed from those for Graves' disease alone. In 7 APS III patients with both autoimmune thyroid diseases and pituitary disorders (group C), the haplotype frequency of HLA DRB1*0405-DQA1*0303-DQB1*0401 was significantly higher than in controls.
  
  
  CONCLUSIONS
  Susceptible HLA class II haplotypes of DRB1-DQA1-DQB1 for APS III differ between the Japanese and Caucasian populations. More interestingly, the susceptible HLA class II haplotypes differ among the three types of Japanese APS III and are not merely a combination of susceptibility haplotypes of each endocrine disease.
authors.affiliation: Department of Endocrinology, Metabolism and Nephrology, Kochi Medical School, Kochi University, Nankoku, Japan. hasimotk@med.kochi-u.ac.jp
authors.forename: Kozo
authors.initials: K
authors.lastname: Hashimoto
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Maruyama
authors.forename: Mitsuru
authors.initials: M
authors.lastname: Nishiyama
authors.forename: Koichi
authors.initials: K
authors.lastname: Asaba
authors.forename: Yukio
authors.initials: Y
authors.lastname: Ikeda
authors.forename: Toshihiro
authors.initials: T
authors.lastname: Takao
authors.forename: Yasumasa
authors.initials: Y
authors.lastname: Iwasaki
authors.forename: Yositaka
authors.initials: Y
authors.lastname: Kumon
authors.forename: Tadashi
authors.initials: T
authors.lastname: Suehiro
authors.forename: Noriyasu
authors.initials: N
authors.lastname: Tanimoto
authors.forename: Miki
authors.initials: M
authors.lastname: Mizobuchi
authors.forename: Tosihiro
authors.initials: T
authors.lastname: Nakamura
mesh_terms: D000328:Adult; D000368:Aged; D000483:Alleles; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006111:Graves Disease / Q000235:genetics; D006683:HLA-DQ Antigens / Q000235:genetics*; D059848:HLA-DQ alpha-Chains; D059866:HLA-DQ beta-Chains; D006684:HLA-DR Antigens / Q000235:genetics*; D059811:HLA-DRB1 Chains; D006239:Haplotypes; D050031:Hashimoto Disease / Q000235:genetics; D006801:Humans; D007564:Japan; D008875:Middle Aged; D016884:Polyendocrinopathies, Autoimmune / Q000235:genetics*
chemical_list: D006683:HLA-DQ Antigens; D059848:HLA-DQ alpha-Chains; D059866:HLA-DQ beta-Chains; C069050:HLA-DQA1 antigen; C069051:HLA-DQB1 antigen; D006684:HLA-DR Antigens; D059811:HLA-DRB1 Chains