Polymorphic amino acid positions of HLA-DRB1 are associated with asparaginase hypersensitivity. (A) Amino acid position 73 had the strongest association with asparaginase hypersensitivity, and positions 11, 13, 14, 25, 30, 57, 60, 74, and 78 were associated with hypersensitivity to a lesser extent. The y-axis shows the permuted P value (P_adjusted) of each association tested and the x-axis represents the amino acid positions of the HLA-DRB1 protein, excluding the leader signal sequence. The dashed horizontal red line identifies a permuted significance threshold of P < .05 that is adjusted for multiple testing. (B) Patients with a glycine (Gly) residue at HLA-DRB1 amino acid position 73 had a higher incidence of hypersensitivity compared with patients with an alanine (Ala/Ala) (n = 1,870, P = 6.45 × 10⁻⁶ [P_adjusted < 1.00 × 10⁻⁴]).