Publication: HLA-B*13 :01 Is a Predictive Marker of Dapsone-Induced Severe Cutaneous Adverse Reactions in Thai Patients
Issued Date
2021-05-04
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16643224
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2-s2.0-85106195756
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Mahidol University
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SCOPUS
Bibliographic Citation
Frontiers in Immunology. Vol.12, (2021)
Suggested Citation
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 HLA-B*13 :01 Is a Predictive Marker of Dapsone-Induced Severe Cutaneous Adverse Reactions in Thai Patients. Frontiers in Immunology. Vol.12, (2021). doi:10.3389/fimmu.2021.661135 Retrieved from: https://repository.li.mahidol.ac.th/handle/20.500.14594/77290
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Title
HLA-B*13 :01 Is a Predictive Marker of Dapsone-Induced Severe Cutaneous Adverse Reactions in Thai Patients
Author(s)
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
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
Other Contributor(s)
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
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
Abstract
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.