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-.
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 |
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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 |
Related URLs: | |
URI: | https://livrepository.liverpool.ac.uk/id/eprint/3147668 |