title: HLA-B*15:21 and carbamazepine-induced Stevens-Johnson syndrome: pooled-data and in silico analysis.
abstract: HLA-B*15:02 screening before carbamazepine (CBZ) prescription in Asian populations is the recommended practice to prevent CBZ-induced Stevens-Johnson syndrome (CBZ-SJS). However, a number of patients have developed CBZ-SJS even having no HLA-B*15:02. Herein, we present the case of a Thai patient who had a negative HLA-B*15:02 screening result but later developed CBZ-SJS. Further HLA typing revealed HLA-B*15:21/B*13:01. HLA-B*15:21 is a member of the HLA-B75 serotype and is commonly found in Southeast Asian populations. Based on this case, we hypothesised that if all HLA-B*15:02 carriers were prevented from CBZ prescription, another common HLA-B75 serotype marker would show its association with CBZ-SJS. To test this hypothesis, we pooled data from previous association studies in Asian populations, excluded all cases with HLA-B*15:02, and analysed the association significance of HLA-B75 serotype markers. A significant association was found between CBZ-SJS and HLA-B*15:21 and HLA-B*15:11. We also applied an in silico analysis and found that all HLA-B75 serotype molecules shared similar capability in binding the CBZ molecule. In summary, this report provides the first evidence of a positive association between HLA-B*15:21 and CBZ-SJS and the first in silico analysis of CBZ binding sites and details of the molecular behaviour of HLA-B75 molecule to explain its molecular action.
authors.affiliation: Department of Pathology, Faculty of Medicine, Prince of Songkla University, Songkhla 90110, Thailand.
authors.forename: Kanoot
authors.initials: K
authors.lastname: Jaruthamsophon
authors.affiliation: Department of Biomedical Sciences, Faculty of Medicine, Prince of Songkla University, Songkhla 90110, Thailand.
authors.forename: Varomyalin
authors.initials: V
authors.lastname: Tipmanee
authors.affiliation: Division of Pharmacy, Songklanagarind Hospital, Faculty of Medicine, Prince of Songkla University, Songkhla 90110, Thailand.
authors.forename: Antida
authors.initials: A
authors.lastname: Sangiemchoey
authors.affiliation: Division of Pharmacogenomics and Personalized Medicine, Department of Pathology, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok 10400, Thailand.|Laboratory for Pharmacogenomics, Somdech Phra Debaratana Medical Center (SDMC), Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok 10400, Thailand.
authors.forename: Chonlaphat
authors.initials: C
authors.lastname: Sukasem
authors.affiliation: Department of Pathology, Faculty of Medicine, Prince of Songkla University, Songkhla 90110, Thailand.
authors.forename: Pornprot
authors.initials: P
authors.lastname: Limprasert
mesh_terms: D000293:Adolescent; D000595:Amino Acid Sequence; D044466:Asian People; D002220:Carbamazepine / Q000009:adverse effects* / Q000378:metabolism; D003198:Computer Simulation; D059910:HLA-B15 Antigen / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D008297:Male; D011485:Protein Binding; D065288:Serogroup; D013262:Stevens-Johnson Syndrome / Q000235:genetics*
chemical_list: C483536:HLA-B*15:02 antigen; D059910:HLA-B15 Antigen; D002220:Carbamazepine