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

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 (P4 3.8 10 5 ) with a significant difference from other amino acid variations (AIC5 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.