氨苯砜引起的严重皮肤药物不良反应与泰国人群中的HLA - B*13:01等位基因密切相关。
Dapsone-induced severe cutaneous adverse drug reactions are strongly linked with HLA-B*13: 01 allele in the Thai population.
作者信息
Tempark Therdpong, Satapornpong Patompong, Rerknimitr Pawinee, Nakkam Nontaya, Saksit Niwat, Wattanakrai Penpun, Jantararoungtong Thawinee, Koomdee Napatrupron, Mahakkanukrauh Ajanee, Tassaneeyakul Wichittra, Suttisai Sumitra, Pratoomwun Jirawat, Klaewsongkram Jettanong, Rerkpattanapipat Ticha, Sukasem Chonlaphat
机构信息
Departments of aPediatrics, Division of Pediatric Dermatology bMedicine, Division of Dermatology, Skin and Allergy Research Unit cMedicine, Division of Allergy and Clinical Immunology, Skin and Allergy Research Unit, Faculty of Medicine, Chulalongkorn University dLaboratory for Pharmacogenomics, Somdech Phra Debaratana Medical Center (SDMC) eDepartment of Pathology, Division of Pharmacogenomics and Personalized Medicine fDepartment of Medicine, Division of Dermatology gDepartment of Medicine, Division of Allergy Immunology and Rheumatology, Faculty of Medicine, Ramathibodi Hospital, Mahidol University hThe Thai Severe Cutaneous Adverse Drug Reaction (THAI-SCAR) Research Group, Bangkok Departments of iPharmacology jMedicine, Faculty of Medicine, Khon Kaen University, Khon Kaen kSchool of Pharmaceutical Sciences, University of Phayao, Phayao lPharmacy Department, Phrae Hospital, Phrae, Thailand.
出版信息
Pharmacogenet Genomics. 2017 Dec;27(12):429-437. doi: 10.1097/FPC.0000000000000306.
OBJECTIVES
A previous publication in Chinese leprosy patients showed that the HLA-B13:01 allele is a strong genetic marker for dapsone-induced drug hypersensitivity reactions, however there are no data describing whether HLA-B13:01 is a valid marker for prediction of dapsone-induced drug hypersensitivity reactions in other ethnicities or nonleprosy patients. The aim of this study is to investigate whether there is an association between HLA genotypes and dapsone-induced severe cutaneous adverse reactions (SCARs) in Thai nonleprosy patients.
PATIENTS AND METHODS
HLA-B genotypes of 15 patients with dapsone-induced SCARs (11 drug reaction with eosinophilia and systemic symptoms, 4 Stevens-Johnson syndrome/toxic epidermal necrolysis), 29 control patients, and 986 subjects from the general Thai population were determined by the reverse PCR sequence-specific oligonucleotides probe.
RESULTS
The HLA-B13:01 allele was significantly associated with dapsone-induced SCARs compared with dapsone-tolerant controls (odds ratio: 54.00, 95% confidence interval: 7.96-366.16, P=0.0001) and the general population (odds ratio: 26.11, 95% confidence interval: 7.27-93.75, P=0.0001). In addition, HLA-B13:01 associated with dapsone-induced SJS-TEN (OR: 40.50, 95% confidence interval: 2.78-591.01, P=0.0070) and DRESS (OR: 60.75, 95% confidence interval: 7.44-496.18, P=0.0001).
CONCLUSION
This study demonstrated an association between HLA-B13:01 and dapsone-induced SCARs including Stevens-Johnson syndrome/toxic epidermal necrolysis and drug reaction with eosinophilia and systemic symptoms in nonleprosy patients. Moreover, these results suggest that the HLA-B13:01 allele may be a useful genetic marker for prediction of dapsone-induced SCARs in Thai and Han-Chinese populations.
目的
之前一项针对中国麻风病患者的研究表明，HLA - B13:01等位基因是氨苯砜诱导的药物超敏反应的一个强遗传标志物，然而，尚无数据描述HLA - B13:01是否是预测其他种族或非麻风病患者氨苯砜诱导的药物超敏反应的有效标志物。本研究的目的是调查泰国非麻风病患者中HLA基因型与氨苯砜诱导的严重皮肤不良反应（SCARs）之间是否存在关联。
患者与方法
采用反向PCR序列特异性寡核苷酸探针法，对15例氨苯砜诱导的SCARs患者（11例伴有嗜酸性粒细胞增多和全身症状的药物反应，4例史蒂文斯 - 约翰逊综合征/中毒性表皮坏死松解症）、29例对照患者以及986名泰国普通人群的HLA - B基因型进行了检测。
结果
与耐氨苯砜的对照患者相比，HLA - B13:01等位基因与氨苯砜诱导的SCARs显著相关（比值比：54.00，95%置信区间：7.96 - 366.16，P = 0.0001），与普通人群相比也显著相关（比值比：26.11，95%置信区间：7.27 - 93.75，P = 0.0001）。此外，HLA - B13:01与氨苯砜诱导的史蒂文斯 - 约翰逊综合征/中毒性表皮坏死松解症（OR：40.50，95%置信区间：2.78 - 591.01，P = 0.0070）和伴有嗜酸性粒细胞增多和全身症状的药物反应（OR：60.75，95%置信区间：7.44 - 496.18，P = 0.0001）相关。
结论
本研究证明了HLA - B13:01与氨苯砜诱导的SCARs之间存在关联，包括非麻风病患者中的史蒂文斯 - 约翰逊综合征/中毒性表皮坏死松解症以及伴有嗜酸性粒细胞增多和全身症状的药物反应。此外，这些结果表明HLA - B13:01等位基因可能是预测泰国人和汉族人群中氨苯砜诱导的SCARs的有用遗传标志物。
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