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- Title
Association of Takayasu arteritis with HLA-B*67:01 and two amino acids in HLA-B protein.
- Authors
Terao, Chikashi; Yoshifuji, Hajime; Ohmura, Koichiro; Murakami, Kosaku; Kawabata, Daisuke; Yurugi, Kimiko; Tazaki, Junichi; Kinoshita, Hideyuki; Kimura, Akinori; Akizuki, Masashi; Kawaguchi, Yasushi; Yamanaka, Hisashi; Miura, Yasuo; Maekawa, Taira; Saji, Hiroo; Mimori, Tsuneyo; Matsuda, Fumihiko
- 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.
- Subjects
JAPAN; VASCULITIS; ACADEMIC medical centers; CHI-squared test; CONFIDENCE intervals; EPIDEMIOLOGY; FISHER exact test; GENES; MULTIVARIATE analysis; RESEARCH funding; STATISTICS; HLA-B27 antigen; LOGISTIC regression analysis; DATA analysis; CASE-control method; DATA analysis software; TAKAYASU arteritis; GENETICS; DISEASE risk factors
- Publication
Rheumatology, 2013, Vol 52, Issue 10, p1769
- ISSN
1462-0324
- Publication type
Article
- DOI
10.1093/rheumatology/ket241