Browsing by Author "Kittipong Wantavornprasert"

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    HLA-B*13 :01 Is a Predictive Marker of Dapsone-Induced Severe Cutaneous Adverse Reactions in Thai Patients
    (2021-05-04) Patompong Satapornpong; Jirawat Pratoomwun; Pawinee Rerknimitr; Jettanong Klaewsongkram; Nontaya Nakkam; Thanyada Rungrotmongkol; Parinya Konyoung; Niwat Saksit; Ajanee Mahakkanukrauh; Warayuwadee Amornpinyo; Usanee Khunarkornsiri; Therdpong Tempark; Kittipong Wantavornprasert; Pimonpan Jinda; Napatrupron Koomdee; Thawinee Jantararoungtong; Ticha Rerkpattanapipat; Chuang Wei Wang; Dean Naisbitt; Wichittra Tassaneeyakul; Manasalak Ariyachaipanich; Thapana Roonghiranwat; Munir Pirmohamed; Wen Hung Chung; Chonlaphat Sukasem; Ramathibodi Hospital; University of Phayao; Xiamen Chang Gung Hospital; Chang Gung Memorial Hospital; Udon Thani Center Hospital; Prapokklao Hospital; Chulalongkorn University; Faculty of Medicine, Khon Kaen University; Rangsit University; King Chulalongkorn Memorial Hospital; University of Liverpool; Faculty of Medicine Ramathibodi Hospital, Mahidol University; Huachiew Chalermprakiet University; Khon Kaen Regional Hospital; Faculty of Medicine, Chulalongkorn University; ANAN Hospital; The Thai Severe Cutaneous Adverse Drug Reaction (THAI-SCAR) Research Group
    HLA-B*13:01 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 HLA 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. HLA class I and II alleles were genotyped using polymerase chain reaction-sequence specific oligonucleotides (PCR-SSOs). CYP2C9, CYP2C19, and CYP3A4 genotypes were determined by the TaqMan real-time PCR assay. We performed computational analyses of dapsone and DDS-NHOH interacting with HLA-B*13:01 and HLA-B*13:02 alleles by the molecular docking approach. Among all the HLA alleles, only HLA-B*13:01 allele was found to be significantly associated with dapsone-induced SCARs (OR = 39.00, 95% CI = 7.67–198.21, p = 5.3447 × 10−7), SJS-TEN (OR = 36.00, 95% CI = 3.19–405.89, p = 2.1657 × 10−3), and DRESS (OR = 40.50, 95% CI = 6.38–257.03, p = 1.0784 × 10−5) as compared to dapsone-tolerant controls. Also, HLA-B*13:01 allele was strongly associated with dapsone-induced SCARs in Asians (OR = 36.00, 95% CI = 8.67–149.52, p = 2.8068 × 10−7) and Taiwanese (OR = 31.50, 95% CI = 4.80–206.56, p = 2.5519 × 10−3). Furthermore, dapsone and DDS-NHOH fit within the extra-deep sub pocket of the antigen-binding site of the HLA-B*13:01 allele and change the antigen-recognition site. However, there was no significant association between genetic polymorphism of cytochrome P450 (CYP2C9, CYP2C19, and CYP3A4) and dapsone-induced SCARs (SJS-TEN and DRESS). The results of this study support the specific genotyping of the HLA-B*13:01 allele to avoid dapsone-induced SCARs including SJS-TEN and DRESS before initiating dapsone therapy in the Asian population.