{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T21:42:30Z","timestamp":1791495750947,"version":"4.3.4"},"reference-count":58,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2021,5,4]],"date-time":"2021-05-04T00:00:00Z","timestamp":1620086400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p>\n                    <jats:italic>HLA-B*13:01<\/jats:italic>\n                    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\n                    <jats:italic>HLA<\/jats:italic>\n                    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.\n                    <jats:italic>HLA<\/jats:italic>\n                    class I and II alleles were genotyped using polymerase chain reaction-sequence specific oligonucleotides (PCR-SSOs).\n                    <jats:italic>CYP2C9<\/jats:italic>\n                    ,\n                    <jats:italic>CYP2C19<\/jats:italic>\n                    , and\n                    <jats:italic>CYP3A4<\/jats:italic>\n                    genotypes were determined by the TaqMan real-time PCR assay. We performed computational analyses of dapsone and DDS-NHOH interacting with\n                    <jats:italic>HLA-B*13:01<\/jats:italic>\n                    and\n                    <jats:italic>HLA-B*13:02<\/jats:italic>\n                    alleles by the molecular docking approach. Among all the\n                    <jats:italic>HLA<\/jats:italic>\n                    alleles, only\n                    <jats:italic>HLA-B*13:01<\/jats:italic>\n                    allele was found to be significantly associated with dapsone-induced SCARs (OR = 39.00, 95% CI = 7.67\u2013198.21, p = 5.3447 \u00d7 10\n                    <jats:sup>\u22127<\/jats:sup>\n                    ), SJS-TEN (OR = 36.00, 95% CI = 3.19\u2013405.89, p = 2.1657 \u00d7 10\n                    <jats:sup>\u22123<\/jats:sup>\n                    ), and DRESS (OR = 40.50, 95% CI = 6.38\u2013257.03, p = 1.0784 \u00d7 10\n                    <jats:sup>\u22125<\/jats:sup>\n                    ) as compared to dapsone-tolerant controls. Also\n                    <jats:italic>, HLA-B*13:01<\/jats:italic>\n                    allele was strongly associated with dapsone-induced SCARs in Asians (OR = 36.00, 95% CI = 8.67\u2013149.52, p = 2.8068 \u00d7 10\n                    <jats:sup>\u22127<\/jats:sup>\n                    ) and Taiwanese (OR = 31.50, 95% CI = 4.80\u2013206.56, p = 2.5519 \u00d7 10\n                    <jats:sup>\u22123<\/jats:sup>\n                    ). Furthermore, dapsone and DDS-NHOH fit within the extra-deep sub pocket of the antigen-binding site of the\n                    <jats:italic>HLA-B*13:01<\/jats:italic>\n                    allele and change the antigen-recognition site. However, there was no significant association between genetic polymorphism of cytochrome P450 (\n                    <jats:italic>CYP2C9<\/jats:italic>\n                    ,\n                    <jats:italic>CYP2C19<\/jats:italic>\n                    , and\n                    <jats:italic>CYP3A4<\/jats:italic>\n                    ) and dapsone-induced SCARs (SJS-TEN and DRESS). The results of this study support the specific genotyping of the\n                    <jats:italic>HLA-B*13:01<\/jats:italic>\n                    allele to avoid dapsone-induced SCARs including SJS-TEN and DRESS before initiating dapsone therapy in the Asian population.\n                  <\/jats:p>","DOI":"10.3389\/fimmu.2021.661135","type":"journal-article","created":{"date-parts":[[2021,5,4]],"date-time":"2021-05-04T11:31:54Z","timestamp":1620127914000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":50,"title":["HLA-B*13 :01 Is a Predictive Marker of Dapsone-Induced Severe Cutaneous Adverse Reactions in Thai Patients"],"prefix":"10.3389","volume":"12","author":[{"given":"Patompong","family":"Satapornpong","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jirawat","family":"Pratoomwun","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pawinee","family":"Rerknimitr","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jettanong","family":"Klaewsongkram","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nontaya","family":"Nakkam","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thanyada","family":"Rungrotmongkol","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Parinya","family":"Konyoung","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Niwat","family":"Saksit","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ajanee","family":"Mahakkanukrauh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Warayuwadee","family":"Amornpinyo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Usanee","family":"Khunarkornsiri","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Therdpong","family":"Tempark","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kittipong","family":"Wantavornprasert","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pimonpan","family":"Jinda","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Napatrupron","family":"Koomdee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thawinee","family":"Jantararoungtong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ticha","family":"Rerkpattanapipat","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chuang-Wei","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dean","family":"Naisbitt","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wichittra","family":"Tassaneeyakul","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manasalak","family":"Ariyachaipanich","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thapana","family":"Roonghiranwat","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Munir","family":"Pirmohamed","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wen-Hung","family":"Chung","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chonlaphat","family":"Sukasem","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2021,5,4]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1067\/mjd.2001.114733","article-title":"Dapsone 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