Yuliwulandari Rika, Kristin Erna, Prayuni Kinasih, Sachrowardi Qomariyah, Suyatna Franciscus D, Menaldi Sri Linuwih, Wichukchinda Nuanjun, Mahasirimongkol Surakameth, Cavallari Larisa H
Department of Pharmacology, Faculty of Medicine, YARSI University, Cempaka Putih, Jakarta Pusat, DKI Jakarta, Indonesia.
Genomic Medicine Research Centre, YARSI Research Institute, YARSI University, Cempaka Putih, Jakarta Pusat, DKI Jakarta, Indonesia.
Pharmacogenomics. 2017 Dec;18(18):1643-1648. doi: 10.2217/pgs-2017-0103. Epub 2017 Oct 20.
Carbamazepine (CBZ) is a common cause of life-threatening cutaneous adverse drug reactions such as Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN). Previous studies have reported a strong association between the HLA genotype and CBZ-induced SJS/TEN. We investigated the association between the HLA genotype and CBZ-induced SJS/TEN in Javanese and Sundanese patients in Indonesia. Nine unrelated patients with CBZ-induced SJS/TEN and 236 healthy Javanese and Sundanese controls were genotyped for HLA-B and their allele frequencies were compared. The HLA-B15:02 allele was found in 66.7% of the patients with CBZ-induced SJS/TEN, but only in 29.4% of tolerant control (p = 0.029; odds ratio [OR]: 6.5; 95% CI: 1.2-33.57) and 22.9% of healthy controls (p = 0.0021; OR: 6.78; 95% CI: 1.96-23.38). These findings support the involvement of HLA-B15:02 in CBZ-induced SJS/TEN reported in other Asian populations. Interestingly, we also observed the presence of the HLA-B15:21 allele. HLA-B15:02 and HLA-B*15:21 are members of the HLA-B75 serotype, for which a greater frequency was observed in CBZ-induced SJS/TEN (vs tolerant control [p = 0.0078; OR: 12; 95% CI: 1.90-75.72] and vs normal control [p = 0.0018; OR: 8.56; 95% CI: 1.83-40]). Our findings suggest that screening for the HLA-B75 serotype can predict the risk of CBZ-induced SJS/TEN more accurately than screening for a specific allele.
卡马西平（CBZ）是史蒂文斯 - 约翰逊综合征（SJS）和中毒性表皮坏死松解症（TEN）等危及生命的皮肤药物不良反应的常见诱因。既往研究报道了HLA基因型与CBZ诱导的SJS/TEN之间存在密切关联。我们调查了印度尼西亚爪哇族和巽他族患者中HLA基因型与CBZ诱导的SJS/TEN之间的关联。对9例无关的CBZ诱导的SJS/TEN患者以及236名健康的爪哇族和巽他族对照进行HLA - B基因分型，并比较其等位基因频率。在66.7%的CBZ诱导的SJS/TEN患者中发现了HLA - B15:02等位基因，但在耐受性对照中仅为29.4%（p = 0.029；优势比[OR]：6.5；95%置信区间：1.2 - 33.57），在健康对照中为22.9%（p = 0.0021；OR：6.78；95%置信区间：1.96 - 23.38）。这些发现支持了HLA - B15:02参与其他亚洲人群中CBZ诱导的SJS/TEN的报道。有趣的是，我们还观察到了HLA - B15:21等位基因的存在。HLA - B15:02和HLA - B*15:21属于HLA - B75血清型，在CBZ诱导的SJS/TEN中观察到其频率更高（与耐受性对照相比[p = 0.0078；OR：12；95%置信区间：1.90 - 75.72]，与正常对照相比[p = 0.0018；OR：8.56；95%置信区间：1.83 - 40]）。我们的研究结果表明，筛查HLA - B75血清型比筛查特定等位基因能更准确地预测CBZ诱导的SJS/TEN的风险。
