Association between HLA-B Alleles and Carbamazepine-Induced Maculopapular Exanthema and Severe Cutaneous Reactions in Thai Patients

Chonlaphat Sukasem; Chonlawat Chaichan; Thapanat Nakkrut; Patompong Satapornpong; Kanoot Jaruthamsophon; Thawinee Jantararoungtong; Napatrupron Koomdee; Suthida Sririttha; Sadeep Medhasi; Sarawut Oo-Puthinan; Ticha Rerkpattanapipat; Jettanong Klaewsongkram; Pawinee Rerknimitr; Papapit Tuchinda; Leena Chularojanamontri; Napatra Tovanabutra; Apichaya Puangpetch; Wichai Aekplakorn

doi:10.1155/2018/2780272

Association between HLA-B Alleles and Carbamazepine-Induced Maculopapular Exanthema and Severe Cutaneous Reactions in Thai Patients

J Immunol Res. 2018 Jan 10:2018:2780272. doi: 10.1155/2018/2780272. eCollection 2018.

Authors

Chonlaphat Sukasem^{1

2

3

4}, Chonlawat Chaichan^{1

2}, Thapanat Nakkrut^{5

6}, Patompong Satapornpong^{1

2}, Kanoot Jaruthamsophon⁷, Thawinee Jantararoungtong^{1

2}, Napatrupron Koomdee^{1

2}, Suthida Sririttha^{1

2

8}, Sadeep Medhasi⁹, Sarawut Oo-Puthinan⁵, Ticha Rerkpattanapipat^{4

10}, Jettanong Klaewsongkram^{4

11}, Pawinee Rerknimitr^{4

12}, Papapit Tuchinda^{4

13}, Leena Chularojanamontri^{4

13}, Napatra Tovanabutra^{4

14}, Apichaya Puangpetch^{1

2}, Wichai Aekplakorn¹⁵

Affiliations

¹ Division of Pharmacogenomics and Personalized Medicine, Department of Pathology, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok, Thailand.
² Laboratory for Pharmacogenomics, Somdech Phra Debaratana Medical Center (SDMC), Ramathibodi Hospital, Bangkok, Thailand.
³ Ramathibodi Multidisciplinary Epilepsy Center, Faculty of Medicine, Ramathibodi Hospital, Mahidol University, Bangkok, Thailand.
⁴ The Thai Severe Cutaneous Adverse Drug Reaction (THAI-SCAR) Research Group, Bangkok, Thailand.
⁵ Department of Pharmacy Practice, Faculty of Pharmaceutical Sciences, Naresuan University, Phitsanulok, Thailand.
⁶ Department of Pharmacy, Prasat Neurological Institute, Bangkok, Thailand.
⁷ Department of Pathology, Faculty of Medicine, Prince of Songkla University, Songkla, Thailand.
⁸ Department of Clinical Pharmacy Practice, Faculty of Pharmacy, Mahidol University, Bangkok, Thailand.
⁹ School of Medicine, Mae Fah Luang University, Chiang Rai, Thailand.
¹⁰ Division of Allergy Immunology and Rheumatology, Department of Medicine, Faculty of Medicine, Ramathibodi Hospital, Mahidol University, Bangkok, Thailand.
¹¹ Division of Allergy and Clinical Immunology, Skin and Allergy Research Unit, Department of Medicine, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand.
¹² Division of Dermatology, Skin and Allergy Research Unit, Department of Medicine, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand.
¹³ Department of Dermatology, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand.
¹⁴ Dermatological Division, Department of Internal Medicine, Chiang Mai University, Chiang Mai, Thailand.
¹⁵ Department of Community Medicine, Ramathibodi Hospital, Mahidol University, Bangkok, Thailand.

Abstract

The HLA-B∗15:02 allele has been reported to have a strong association with carbamazepine-induced Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN) in Thai patients. The HLA-B alleles associated with carbamazepine-induced maculopapular exanthema (MPE) and the drug reaction with eosinophilia and systemic symptoms (DRESS) among the Thai population have never been reported. The aim of the present study was to carry out an analysis of the involvement of HLA-B alleles in carbamazepine-induced cutaneous adverse drug reactions (cADRs) in the Thai population. A case-control study was performed by genotyping the HLA-B alleles of Thai carbamazepine-induced hypersensitivity reaction patients (17 MPE, 16 SJS/TEN, and 5 DRESS) and 271 carbamazepine-tolerant controls. We also recruited 470 healthy Thai candidate subjects who had not taken carbamazepine. HLA-B∗15:02 showed a significant association with carbamazepine-induced MPE (P = 0.0022, odds ratio (OR) (95% confidence interval [CI]) = 7.27 (2.04-25.97)) and carbamazepine-induced SJS/TEN (P = 4.46 × 10^-13; OR (95% CI) = 70.91(19.67-255.65)) when compared with carbamazepine-tolerant controls. Carbamazepine-induced SJS/TEN also showed an association with HLA-B∗15:21 allele (P = 0.013; OR (95% CI) = 9.54 (1.61-56.57)) when compared with carbamazepine-tolerant controls. HLA-B∗58:01 allele was significantly related to carbamazepine-induced MPE (P = 0.007; OR (95% CI) = 4.73 (1.53-14.66)) and DRESS (P = 0.0315; OR (95% CI) = 7.55 (1.20-47.58)) when compared with carbamazepine-tolerant controls. These alleles may serve as markers to predict carbamazepine-induced cADRs in the Thai population.

MeSH terms

Adolescent
Adult
Alleles
Carbamazepine / adverse effects*
Carbamazepine / therapeutic use
Case-Control Studies
Child
Drug Eruptions / genetics*
Drug Hypersensitivity Syndrome / genetics*
Female
Gene Frequency
Genetic Association Studies
Genotype*
HLA-B Antigens / genetics*
HLA-B15 Antigen / genetics*
Humans
Male
Middle Aged
Polymorphism, Genetic
Skin / pathology
Stevens-Johnson Syndrome / genetics*
Thailand
Young Adult

Substances

HLA-B Antigens
HLA-B*15:02 antigen
HLA-B*58:01 antigen
HLA-B15 Antigen
Carbamazepine