Chang C-C, Ng C-C, Too C-L, Choon S-E, Lee C-K, Chung W-H, Hussein S H, Lim K-S, Murad S
Department of Dermatology, Kuala Lumpur Hospital, Kuala Lumpur, Malaysia.
Faculty of Science, Institute of Biological Sciences, University of Malaya, Kuala Lumpur, Malaysia.
Pharmacogenomics J. 2017 Mar;17(2):170-173. doi: 10.1038/tpj.2016.10. Epub 2016 Mar 1.
Phenytoin (PHT) is a common cause of severe cutaneous adverse reactions (SCARs), including Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN) and drug reaction with eosinophilia and systemic symptoms (DRESS). Although HLA-B15:02 is associated with PHT-induced SJS/TEN (PHT-SJS/TEN) in Han Chinese and Thais, the genetic basis for susceptibility to PHT-induced SCARs (PHT-SCAR) in other populations remains unclear. We performed a case-control association study by genotyping the human leukocyte antigen (HLA)-B alleles of 16 Malay PHT-SCAR patients (13 SJS/TEN and 3 DRESS), 32 PHT-tolerant controls and 300 healthy ethnicity-matched controls. A novel genetic biomarker, HLA-B15:13, showed significant association with PHT-SJS/TEN (53.8%, 7/13 cases) (odds ratio (OR) 11.28, P=0.003) and PHT-DRESS (100%, 3/3 cases) (OR 59.00, P=0.003) when compared with PHT-tolerant controls (9.4%, 3/32 controls). We also confirmed HLA-B*15:02 association with PHT-SJS/TEN (61.5%, 8/13 cases vs 21.9%, 7/32 controls; OR 5.71, P=0.016) when compared with PHT-tolerant controls. These alleles may serve as markers to predict PHT-SCAR in Malays.
苯妥英（PHT）是严重皮肤不良反应（SCARs）的常见病因，包括史蒂文斯-约翰逊综合征（SJS）、中毒性表皮坏死松解症（TEN）以及伴有嗜酸性粒细胞增多和全身症状的药物反应（DRESS）。尽管HLA-B15:02与汉族和泰国人中PHT诱导的SJS/TEN（PHT-SJS/TEN）相关，但其他人群中PHT诱导的SCARs（PHT-SCAR）易感性的遗传基础仍不清楚。我们通过对16例马来PHT-SCAR患者（13例SJS/TEN和3例DRESS）、32例PHT耐受对照以及300例种族匹配的健康对照进行人类白细胞抗原（HLA）-B等位基因基因分型，开展了一项病例对照关联研究。一种新的遗传生物标志物HLA-B15:13，与PHT耐受对照（9.4%，3/32对照）相比，与PHT-SJS/TEN（53.8%，7/13例）（比值比（OR）11.28，P = 0.003）和PHT-DRESS（100%，3/3例）（OR 59.00，P = 0.003）显著相关。与PHT耐受对照相比，我们还证实了HLA-B*15:02与PHT-SJS/TEN相关（61.5%，8/13例 vs 21.9%，7/32对照；OR 5.71，P = 0.016）。这些等位基因可作为预测马来人PHT-SCAR的标志物。
