title: Genotyping of relapsing polychondritis identified novel susceptibility HLA alleles and distinct genetic characteristics from other rheumatic diseases.
abstract: To uncover the genetic background of relapsing polychondritis (RPC), a rare autoimmune disease with unknown mechanisms characterized by systemic inflammation of the cartilage, to deepen our understanding of the pathophysiology of RPC and show its distinct genetic characteristics from other rheumatic diseases.
  
  
  
  A total of 102 patients with RPC and 1000 healthy subjects were recruited for a two-staged genetic association study and genotyped for six HLA classical loci. Haplotype association tests were also performed. The associations of amino acid (AA) residues and positions with susceptibility to RPC were analysed. Frequencies of representative susceptibility HLA alleles to other rheumatic diseases in RPC were also analysed.
  
  
  
  HLA-DRB1*16:02, HLA-DQB1*05:02 and HLA-B*67:01, which are in linkage disequilibrium with each other, were associated with RPC (P = 1.9 × 10(-6), 1.4 × 10(-5) and 0.00024, respectively). AA residue at position 57 in HLA-DQB1, the most significant position in type I diabetes mellitus, showed the strongest association among AA residues. HLA-DR4, a known susceptibility allele in Germans, showed a trend of susceptibility association without significance (P = 0.067). No associations were observed between the three alleles and clinical phenotypes. Representative susceptibility HLA alleles to RA, SLE, Behçet disease and Takayasu arteritis did not show enrichment in RPC in spite of sufficient statistical power.
  
  
  
  HLA-DRB1*16:02, HLA-DQB1*05:02 and HLA-B*67:01, in linkage disequilibrium with each other, are associated with susceptibility to RPC Importance of HLA-class II loci in RPC susceptibility is suggested. RPC is considered a genetically distinct disease from other rheumatic diseases.
authors.affiliation: Center for Genomic Medicine, Kyoto University Graduate School of Medicine Center for the Promotion of Interdisciplinary Education and Research, Kyoto University, Kyoto, Japan Division of Rheumatology, Immunology, and Allergy Division of Genetics, Brigham and Women's Hospital, Harvard Medical School, Boston Program in Medical and Population Genetics, Broad Institute, Cambridge, MA, USA a0001101@kuhp.kyoto-u.ac.jp.
authors.forename: Chikashi
authors.initials: C
authors.lastname: Terao
authors.affiliation: Department of Rheumatology and Clinical Immunology, Kyoto University Graduate School of Medicine, Kyoto.
authors.forename: Hajime
authors.initials: H
authors.lastname: Yoshifuji
authors.affiliation: Department of Rare Diseases Research, Institute of Medical Science, St. Marianna University School of Medicine, Kanagawa.
authors.forename: Yoshihisa
authors.initials: Y
authors.lastname: Yamano
authors.affiliation: HLA Laboratory.
authors.forename: Hiroto
authors.initials: H
authors.lastname: Kojima
authors.affiliation: Department of Transfusion Medicine and Cell Therapy, Kyoto University Hospital, Kyoto.
authors.forename: Kimiko
authors.initials: K
authors.lastname: Yurugi
authors.affiliation: Department of Transfusion Medicine and Cell Therapy, Kyoto University Hospital, Kyoto.
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Miura
authors.affiliation: Department of Transfusion Medicine and Cell Therapy, Kyoto University Hospital, Kyoto.
authors.forename: Taira
authors.initials: T
authors.lastname: Maekawa
authors.affiliation: Division of Respiratory and Infectious Diseases, Department of Internal Medicine, St. Marianna University School of Medicine, Kanagawa, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Handa
authors.affiliation: Department of Rheumatology and Clinical Immunology, Kyoto University Graduate School of Medicine, Kyoto.
authors.forename: Koichiro
authors.initials: K
authors.lastname: Ohmura
authors.affiliation: HLA Laboratory.
authors.forename: Hiroh
authors.initials: H
authors.lastname: Saji
authors.affiliation: Department of Rheumatology and Clinical Immunology, Kyoto University Graduate School of Medicine, Kyoto.
authors.forename: Tsuneyo
authors.initials: T
authors.lastname: Mimori
authors.affiliation: Center for Genomic Medicine, Kyoto University Graduate School of Medicine.
authors.forename: Fumihiko
authors.initials: F
authors.lastname: Matsuda
mesh_terms: D000328:Adult; D017668:Age of Onset; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics; D005838:Genotype; D015235:HLA-B Antigens / Q000235:genetics*; D059866:HLA-DQ beta-Chains / Q000235:genetics*; D059811:HLA-DRB1 Chains / Q000235:genetics*; D006801:Humans; D015810:Linkage Disequilibrium / Q000235:genetics; D008297:Male; D011081:Polychondritis, Relapsing / Q000235:genetics*; D012216:Rheumatic Diseases / Q000235:genetics*
chemical_list: D015235:HLA-B Antigens; D059866:HLA-DQ beta-Chains; C069051:HLA-DQB1 antigen; D059811:HLA-DRB1 Chains
keywords: HLA; genetics; relapsing polychondritis