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

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

doi:10.3389/fimmu.2021.661135

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

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^*

^*Corresponding author for this work

Research output: Contribution to journal › Journal Article › peer-review

41 Scopus citations

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.

Original language	English
Article number	661135
Journal	Frontiers in Immunology
Volume	12
DOIs	https://doi.org/10.3389/fimmu.2021.661135
State	Published - 04 05 2021
Externally published	Yes

Bibliographical note

Publisher Copyright:
© Copyright © 2021 Satapornpong, Pratoomwun, Rerknimitr, Klaewsongkram, Nakkam, Rungrotmongkol, Konyoung, Saksit, Mahakkanukrauh, Amornpinyo, Khunarkornsiri, Tempark, Wantavornprasert, Jinda, Koomdee, Jantararoungtong, Rerkpattanapipat, Wang, Naisbitt, Tassaneeyakul, Ariyachaipanich, Roonghiranwat, Pirmohamed, Chung and Sukasem.

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being

Keywords

HLA class I and II alleles
HLA-B*13:01
Thais and Taiwaneses
cytochrome P450
dapsone-induced severe cutaneous adverse reactions

Access to Document

10.3389/fimmu.2021.661135

Cite this

Satapornpong, P., Pratoomwun, J., Rerknimitr, P., Klaewsongkram, J., Nakkam, N., Rungrotmongkol, T., Konyoung, P., Saksit, N., Mahakkanukrauh, A., Amornpinyo, W., Khunarkornsiri, U., Tempark, T., Wantavornprasert, K., Jinda, P., Koomdee, N., Jantararoungtong, T., Rerkpattanapipat, T., Wang, C. W., Naisbitt, D., ... Sukasem, C. (2021). HLA-B*13 :01 Is a Predictive Marker of Dapsone-Induced Severe Cutaneous Adverse Reactions in Thai Patients. Frontiers in Immunology, 12, Article 661135. https://doi.org/10.3389/fimmu.2021.661135

@article{af9fac3aeb3a4e2b9ff7d04c7d1e896e,

title = "HLA-B*13 :01 Is a Predictive Marker of Dapsone-Induced Severe Cutaneous Adverse Reactions in Thai Patients",

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.",

keywords = "HLA class I and II alleles, HLA-B*13:01, Thais and Taiwaneses, cytochrome P450, dapsone-induced severe cutaneous adverse reactions",

author = "Patompong Satapornpong and Jirawat Pratoomwun and Pawinee Rerknimitr and Jettanong Klaewsongkram and Nontaya Nakkam and Thanyada Rungrotmongkol and Parinya Konyoung and Niwat Saksit and Ajanee Mahakkanukrauh and Warayuwadee Amornpinyo and Usanee Khunarkornsiri and Therdpong Tempark and Kittipong Wantavornprasert and Pimonpan Jinda and Napatrupron Koomdee and Thawinee Jantararoungtong and Ticha Rerkpattanapipat and Wang, \{Chuang Wei\} and Dean Naisbitt and Wichittra Tassaneeyakul and Manasalak Ariyachaipanich and Thapana Roonghiranwat and Munir Pirmohamed and Chung, \{Wen Hung\} and Chonlaphat Sukasem",

note = "Publisher Copyright: {\textcopyright} Copyright {\textcopyright} 2021 Satapornpong, Pratoomwun, Rerknimitr, Klaewsongkram, Nakkam, Rungrotmongkol, Konyoung, Saksit, Mahakkanukrauh, Amornpinyo, Khunarkornsiri, Tempark, Wantavornprasert, Jinda, Koomdee, Jantararoungtong, Rerkpattanapipat, Wang, Naisbitt, Tassaneeyakul, Ariyachaipanich, Roonghiranwat, Pirmohamed, Chung and Sukasem.",

year = "2021",

month = may,

day = "4",

doi = "10.3389/fimmu.2021.661135",

language = "英语",

volume = "12",

journal = "Frontiers in Immunology",

issn = "1664-3224",

publisher = "Frontiers Media SA",

}

Satapornpong, P, Pratoomwun, J, Rerknimitr, P, Klaewsongkram, J, Nakkam, N, Rungrotmongkol, T, Konyoung, P, Saksit, N, Mahakkanukrauh, A, Amornpinyo, W, Khunarkornsiri, U, Tempark, T, Wantavornprasert, K, Jinda, P, Koomdee, N, Jantararoungtong, T, Rerkpattanapipat, T, Wang, CW, Naisbitt, D, Tassaneeyakul, W, Ariyachaipanich, M, Roonghiranwat, T, Pirmohamed, M, Chung, WH & Sukasem, C 2021, 'HLA-B*13 :01 Is a Predictive Marker of Dapsone-Induced Severe Cutaneous Adverse Reactions in Thai Patients', Frontiers in Immunology, vol. 12, 661135. https://doi.org/10.3389/fimmu.2021.661135

TY - JOUR

T1 - HLA-B*13 :01 Is a Predictive Marker of Dapsone-Induced Severe Cutaneous Adverse Reactions in Thai Patients

AU - Satapornpong, Patompong

AU - Pratoomwun, Jirawat

AU - Rerknimitr, Pawinee

AU - Klaewsongkram, Jettanong

AU - Nakkam, Nontaya

AU - Rungrotmongkol, Thanyada

AU - Konyoung, Parinya

AU - Saksit, Niwat

AU - Mahakkanukrauh, Ajanee

AU - Amornpinyo, Warayuwadee

AU - Khunarkornsiri, Usanee

AU - Tempark, Therdpong

AU - Wantavornprasert, Kittipong

AU - Jinda, Pimonpan

AU - Koomdee, Napatrupron

AU - Jantararoungtong, Thawinee

AU - Rerkpattanapipat, Ticha

AU - Wang, Chuang Wei

AU - Naisbitt, Dean

AU - Tassaneeyakul, Wichittra

AU - Ariyachaipanich, Manasalak

AU - Roonghiranwat, Thapana

AU - Pirmohamed, Munir

AU - Chung, Wen Hung

AU - Sukasem, Chonlaphat

N1 - Publisher Copyright: © Copyright © 2021 Satapornpong, Pratoomwun, Rerknimitr, Klaewsongkram, Nakkam, Rungrotmongkol, Konyoung, Saksit, Mahakkanukrauh, Amornpinyo, Khunarkornsiri, Tempark, Wantavornprasert, Jinda, Koomdee, Jantararoungtong, Rerkpattanapipat, Wang, Naisbitt, Tassaneeyakul, Ariyachaipanich, Roonghiranwat, Pirmohamed, Chung and Sukasem.

PY - 2021/5/4

Y1 - 2021/5/4

N2 - 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.

AB - 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.

KW - HLA class I and II alleles

KW - HLA-B13:01

KW - Thais and Taiwaneses

KW - cytochrome P450

KW - dapsone-induced severe cutaneous adverse reactions

UR - https://www.scopus.com/pages/publications/85106195756

U2 - 10.3389/fimmu.2021.661135

DO - 10.3389/fimmu.2021.661135

M3 - 文章

C2 - 34017337

AN - SCOPUS:85106195756

SN - 1664-3224

VL - 12

JO - Frontiers in Immunology

JF - Frontiers in Immunology

M1 - 661135

ER -

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

Abstract

Bibliographical note

UN SDGs

Keywords

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