<i>HLA-B*13:01</i> Is a Predictive Marker of Dapsone-Induced Severe Cutaneous Adverse Reactions in Thai Patients



Satapornpong, Patompong, Pratoomwun, Jirawat, Rerknimitr, Pawinee, Klaewsongkram, Jettanong, Nakkam, Nontaya, Rungrotmongkol, Thanyada, Konyoung, Parinya, Saksit, Niwat, Mahakkanukrauh, Ajanee, Amornpinyo, Warayuwadee
et al (show 15 more authors) (2021) <i>HLA-B*13:01</i> Is a Predictive Marker of Dapsone-Induced Severe Cutaneous Adverse Reactions in Thai Patients. FRONTIERS IN IMMUNOLOGY, 12. 661135-.

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Abstract

<i>HLA-B*13:01</i> allele has been identified as the genetic determinant of dapsone hypersensitivity syndrome (DHS) among leprosy and non-leprosy patients in several studies. Dapsone hydroxylamine (DDS-NHOH), an active metabolite of dapsone, has been believed to be responsible for DHS. However, studies have not highlighted the importance of other genetic polymorphisms in dapsone-induced severe cutaneous adverse reactions (SCAR). We investigated the association of <i>HLA</i> alleles and cytochrome P450 (CYP) alleles with dapsone-induced SCAR in Thai non-leprosy patients. A prospective cohort study, 16 Thai patients of dapsone-induced SCARs (5 SJS-TEN and 11 DRESS) and 9 Taiwanese patients of dapsone-induced SCARs (2 SJS-TEN and 7 DRESS), 40 dapsone-tolerant controls, and 470 general Thai population were enrolled. <i>HLA</i> class I and II alleles were genotyped using polymerase chain reaction-sequence specific oligonucleotides (PCR-SSOs). <i>CYP2C9</i>, <i>CYP2C19</i>, and <i>CYP3A4</i> genotypes were determined by the TaqMan real-time PCR assay. We performed computational analyses of dapsone and DDS-NHOH interacting with <i>HLA-B*13:01</i> and <i>HLA-B*13:02</i> alleles by the molecular docking approach. Among all the <i>HLA</i> alleles, only <i>HLA-B*13:01</i> allele was found to be significantly associated with dapsone-induced SCARs (OR = 39.00, 95% CI = 7.67-198.21, p = 5.3447 × 10<sup>-7</sup>), SJS-TEN (OR = 36.00, 95% CI = 3.19-405.89, p = 2.1657 × 10<sup>-3</sup>), and DRESS (OR = 40.50, 95% CI = 6.38-257.03, p = 1.0784 × 10<sup>-5</sup>) as compared to dapsone-tolerant controls. Also<i>, HLA-B*13:01</i> allele was strongly associated with dapsone-induced SCARs in Asians (OR = 36.00, 95% CI = 8.67-149.52, p = 2.8068 × 10<sup>-7</sup>) and Taiwanese (OR = 31.50, 95% CI = 4.80-206.56, p = 2.5519 × 10<sup>-3</sup>). Furthermore, dapsone and DDS-NHOH fit within the extra-deep sub pocket of the antigen-binding site of the <i>HLA-B*13:01</i> allele and change the antigen-recognition site. However, there was no significant association between genetic polymorphism of cytochrome P450 (<i>CYP2C9</i>, <i>CYP2C19</i>, and <i>CYP3A4</i>) and dapsone-induced SCARs (SJS-TEN and DRESS). The results of this study support the specific genotyping of the <i>HLA-B*13:01</i> allele to avoid dapsone-induced SCARs including SJS-TEN and DRESS before initiating dapsone therapy in the Asian population.

Item Type: Article
Uncontrolled Keywords: dapsone-induced severe cutaneous adverse reactions, HLA class I and II alleles, HLA-B*13, 01, cytochrome P450, Thais and Taiwaneses
Divisions: Faculty of Health and Life Sciences
Faculty of Health and Life Sciences > Institute of Systems, Molecular and Integrative Biology
Depositing User: Symplectic Admin
Date Deposited: 27 Jan 2022 09:15
Last Modified: 18 Oct 2023 08:37
DOI: 10.3389/fimmu.2021.661135
Open Access URL: https://doi.org/10.3389/fimmu.2021.661135
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URI: https://livrepository.liverpool.ac.uk/id/eprint/3147668