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

作者：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

来源：Rheumatology, 2013, 52(10): 1769-1774.

DOI：10.1093/rheumatology/ket241

• Takayasu arteritis
• genetic association study
• HLA-B
• aortitis
• vasculitis

Objective. Takayasu arteritis (TAK) is a rare autoimmune arteritis that affects large arteries. Although the association between TAK and HLA-B(star)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(star)52:01 and to identify important amino acids of HLA-B protein in TAK susceptibility. %26lt;br%26gt;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. %26lt;br%26gt;Results. Strong associations of susceptibility to TAK with HLA-B(star)52: 01 and HLA-B(star)67:01 were observed (P = 1.0 x 10(-16) and 9.5 x 10(-6), respectively). An independent susceptibility effect of HLA-B(star)67: 01 from HLA-B(star)52: 01 was also detected (P = 1.8 x 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 %26lt;= 3.8 x 10(-5)) with a significant difference from other amino acid variations (Delta AIC %26gt;= 9.65). %26lt;br%26gt;Conclusion. HLA-B(star)67: 01 is associated with TAK independently from HLA-B(star)52:01. Two amino acids in HLA-B protein are strongly associated with TAK susceptibility.

• 出版日期2013-10