Amino Acid Variants of HLA-DRB1 Confer Susceptibility to Dapsone Hypersensitivity Syndrome in Addition to HLA-B*13:01  Zhenhua Yue, Yonghu Sun, Chuan Wang, Wenjun Yu, Jing Cao, Fangfang Bao, Zhenzhen Wang, Hong Liu, Furen Zhang  Journal of Investigative Dermatology  Volume 138, Issue 5, Pages 1101-1106 (May 2018) DOI: 10.1016/j.jid.2017.11.027 Copyright © 2017 The Authors Terms and Conditions

Figure 1 Power calculation based on sample size. Statistical power was calculated on the basis of the sample size (103 DHS patients and 857 DDS-tolerant control individuals) with P-value of the significance threshold (0.05/138). Curves in blue, green, black, and red present statistical power calculated with OR = 2.5, OR = 2.0, OR = 1.8, and OR = 1.5, respectively. The vertical red line shows the MAF threshold of 15%. The statistical power is lower than 50% to discover those variants with MAF ＜ 15% at OR = 2.0. DDS, dapsone; DHS, dapsone hypersensitivity syndrome; MAF, minor allele frequency; OR, odds ratio. Journal of Investigative Dermatology 2018 138, 1101-1106DOI: (10.1016/j.jid.2017.11.027) Copyright © 2017 The Authors Terms and Conditions

Figure 2 Association of HLA-DRB1 amino acid positions with dapsone hypersensitivity syndrome. (a) The five amino acid positions (133, 142, –17, 11, and 13) located in HLA-DRB1 were significantly associated with dapsone hypersensitivity. The red line indicates the significance threshold. (b) No amino acid position was associated with dapsone hypersensitivity after conditioning on position 133. (c) Presentation of amino acid positions of the structure of DRB1. Dark blue shows the β chain of HLA-DR. Positions 11 and 13 occupied the surface of the epitope-binding groove of HLA-DR molecule (PDB ID: 5JLZ). OR, odds ratio. Journal of Investigative Dermatology 2018 138, 1101-1106DOI: (10.1016/j.jid.2017.11.027) Copyright © 2017 The Authors Terms and Conditions

Figure 3 Sequence differences between 12 subtypes of HLA-B*13:01 at six-digit resolution. The x-axis represents numbering of codons (nucleotide sequence displayed in codons); the y-axis represents the six-digit resolution of the HLA-B*13:01 genotype. The dots represent the point mutation harboring of each six-digit HLA-B*13:01 genotype. Journal of Investigative Dermatology 2018 138, 1101-1106DOI: (10.1016/j.jid.2017.11.027) Copyright © 2017 The Authors Terms and Conditions