title: Association of Takayasu arteritis with HLA-B 67:01 and two amino acids in HLA-B protein.
abstract: OBJECTIVE
  Takayasu arteritis (TAK) is a rare autoimmune arteritis that affects large arteries. Although the association between TAK and HLA-B 52:01 is established, the other susceptibility HLA-B alleles are not fully known. We performed genetic association studies to determine independent HLA-B susceptibility alleles other than HLA-B 52:01 and to identify important amino acids of HLA-B protein in TAK susceptibility.
  
  
  METHODS
  One hundred patients with TAK and 1000 unrelated healthy controls were genotyped for HLA-B alleles in the first set, followed by a replication set containing 73 patients with TAK and 1000 controls to compare the frequencies of HLA-B alleles. Step-up logistic regression analysis was performed to identify susceptibility amino acids of HLA-B protein.
  
  
  RESULTS
  Strong associations of susceptibility to TAK with HLA-B 52:01 and HLA-B 67:01 were observed (P = 1.0 × 10(-16) and 9.5 × 10(-6), respectively). An independent susceptibility effect of HLA-B 67:01 from HLA-B 52:01 was also detected (P = 1.8 × 10(-7)). Amino acid residues of histidine at position 171 and phenylalanine at position 67, both of which are located in antigen binding grooves of the HLA-B protein, were associated with TAK susceptibility (P ≤ 3.8 × 10(-5)) with a significant difference from other amino acid variations (ΔAIC ≥ 9.65).
  
  
  CONCLUSIONS
  HLA-B 67:01 is associated with TAK independently from HLA-B 52:01. Two amino acids in HLA-B protein are strongly associated with TAK susceptibility.
authors.affiliation: Center for Genomic Medicine, Kyoto University Graduate School of Medicine, Kyoto 606-8507, Japan. a0001101@kuhp.kyoto-u.ac.jp.
authors.forename: Chikashi
authors.initials: C
authors.lastname: Terao
authors.forename: Hajime
authors.initials: H
authors.lastname: Yoshifuji
authors.forename: Koichiro
authors.initials: K
authors.lastname: Ohmura
authors.forename: Kosaku
authors.initials: K
authors.lastname: Murakami
authors.forename: Daisuke
authors.initials: D
authors.lastname: Kawabata
authors.forename: Kimiko
authors.initials: K
authors.lastname: Yurugi
authors.forename: Junichi
authors.initials: J
authors.lastname: Tazaki
authors.forename: Hideyuki
authors.initials: H
authors.lastname: Kinoshita
authors.forename: Akinori
authors.initials: A
authors.lastname: Kimura
authors.forename: Masashi
authors.initials: M
authors.lastname: Akizuki
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Kawaguchi
authors.forename: Hisashi
authors.initials: H
authors.lastname: Yamanaka
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Miura
authors.forename: Taira
authors.initials: T
authors.lastname: Maekawa
authors.forename: Hiroo
authors.initials: H
authors.lastname: Saji
authors.forename: Tsuneyo
authors.initials: T
authors.lastname: Mimori
authors.forename: Fumihiko
authors.initials: F
authors.lastname: Matsuda
mesh_terms: D000328:Adult; D000368:Aged; D000483:Alleles; D000595:Amino Acid Sequence; D001665:Binding Sites / Q000235:genetics; D016022:Case-Control Studies; D005260:Female; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D005838:Genotype; D015235:HLA-B Antigens / Q000235:genetics*; D059950:HLA-B52 Antigen / Q000235:genetics; D006801:Humans; D008297:Male; D008875:Middle Aged; D008958:Models, Molecular; D013625:Takayasu Arteritis / Q000235:genetics*
chemical_list: D015235:HLA-B Antigens; C501279:HLA-B*52:01 antigen; D059950:HLA-B52 Antigen
keywords: HLA-B; Takayasu arteritis; aortitis; genetic association study; vasculitis