Inserm U946, Saint Louis Hospital, Institut Universitaire d'Hématologie, Université Paris Diderot, Paris, France.
1] Department of Laboratory Medicine, Chang Gung Memorial Hospital, Taoyuan, Taiwan [2] Department of Medical Biotechnology and Laboratory Science, Chang Gung University College of Medicine, Taoyuan, Taiwan.
Pharmacogenomics J. 2014 Jun;14(3):281-8. doi: 10.1038/tpj.2013.40. Epub 2013 Dec 10.
HLA-A31:01 was reported to be associated with carbamazepine (CBZ)-induced severe cutaneous adverse reactions (SCAR), including drug reaction with eosinophilia and systemic symptoms (DRESS), Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN). We conducted an international study using consensus diagnosis criteria to enroll a total of 93 patients with CBZ-SCAR from Europe or Asia. We found that HLA-A31:01 showed a significant association with CBZ-DRESS in Europeans (P<0.001; odds ratio (OR) (95% confidence interval (CI))=57.6 (11.0-340)), and the strong association was also found in Chinese (P<0.001; OR (95% CI)=23.0 (4.2-125)). However, HLA-A31:01 had no association with CBZ-SJS/TEN in neither Chinese nor Europeans. By comparison, HLA-B15:02 showed a strong association with CBZ-SJS/TEN in Chinese (P<0.001, OR (95% CI)=58.1 (17.6-192)). A meta-analysis of this and other published studies confirmed that in all populations, HLA-A31:01 had an extremely strong association with CBZ-DRESS (P<0.001, a pooled OR (95% CI)=13.2 (8.4-20.8)), but a much weaker association with CBZ-SJS/TEN (P=0.01, OR (95% CI)=3.94 (1.4-11.5)). Our data revealed that HLA-A31:01 is a specific predictor for CBZ-DRESS but not for CBZ-SJS/TEN. More studies are needed to investigate the genetic determinant of CBZ-SJS/TEN in Europeans. Considering the potential clinical utility, the cost-effectiveness of the combined HLA-A31:01 and HLA-B15:02 genetic test to prevent CBZ-SCAR in Chinese needs further investigation.
HLA-A31:01 与卡马西平（CBZ）诱导的严重皮肤不良反应（SCAR）有关，包括药物反应伴嗜酸性粒细胞增多和全身症状（DRESS）、史蒂文斯-约翰逊综合征（SJS）和中毒性表皮坏死松解症（TEN）。我们采用共识诊断标准进行了一项国际研究，共纳入来自欧洲或亚洲的 93 例 CBZ-SCAR 患者。我们发现 HLA-A31:01 与欧洲人 CBZ-DRESS 显著相关（P<0.001；比值比（OR）（95%置信区间（CI））=57.6（11.0-340）），在中国人群中也发现了强烈的相关性（P<0.001；OR（95% CI）=23.0（4.2-125））。然而，HLA-A31:01 与中、欧人群的 CBZ-SJS/TEN 均无关。相比之下，HLA-B15:02 与中国人 CBZ-SJS/TEN 显著相关（P<0.001，OR（95% CI）=58.1（17.6-192））。对这项研究和其他已发表研究的荟萃分析证实，在所有人群中，HLA-A31:01 与 CBZ-DRESS 具有极强的相关性（P<0.001，合并 OR（95% CI）=13.2（8.4-20.8）），但与 CBZ-SJS/TEN 的相关性较弱（P=0.01，OR（95% CI）=3.94（1.4-11.5））。我们的数据表明，HLA-A31:01 是 CBZ-DRESS 的特异性预测因子，但不是 CBZ-SJS/TEN 的预测因子。需要进一步研究欧洲人 CBZ-SJS/TEN 的遗传决定因素。鉴于其潜在的临床应用价值，需要进一步研究在中国人群中联合 HLA-A31:01 和 HLA-B15:02 基因检测预防 CBZ-SCAR 的成本效益。
