Association of Takayasu arteritis with HLA-B*67: 01 and two amino acids in HLA-B protein

Chikashi Terao, Hajime Yoshifuji, Koichiro Ohmura, Kosaku Murakami, Daisuke Kawabata, Kimiko Yurugi, Junichi Tazaki, Hideyuki Kinoshita, Akinori Kimura, Masashi Akizuki, Yasushi Kawaguchi, Hisashi Yamanaka, Yasuo Miura, Taira Maekawa, Hiroo Saji, Tsuneyo Mimori, Fumihiko Matsuda

Research output: Contribution to journalArticlepeer-review

34 Citations (Scopus)

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).Conclusion. 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.

Original languageEnglish
Article numberket241
Pages (from-to)1769-1774
Number of pages6
JournalRheumatology (United Kingdom)
Volume52
Issue number10
DOIs
Publication statusPublished - 10-2013
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Rheumatology
  • Pharmacology (medical)

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