HLA-A02:01 allele is associated with tanshinone-induced cutaneous drug reactions in Chinese population
HLA-A02:01 allele is associated with tanshinone-induced cutaneous drug reactions in Chinese population
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HLA-A02:01等位基因与中国人群丹参酮引起的皮肤药物反应相关
DOI：
10.1038/s41397-019-0121-1
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发表时间：
2019
期刊：
影响因子：
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通讯作者：
Qinghe Xing
中科院分区：
文献类型：
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作者：
Qinyuan Zhu;Yanzhou Zhang;Jiekun Xuan;Fanping Yang;Binbin Du;Sheng-an Chen;Sijia Yan;Menglin Jiang;Huizhong Zhu;Hao Xiong;Xiaoqun Luo;Qinghe Xing
丹参酮是一种应用广泛的中成药，虽然经常引起皮肤不良反应(CADR)，但已被证实具有多种药理作用。我们的目的是确定人类白细胞抗原(人类白细胞抗原)I类等位基因是否与丹参酮诱导的中国汉族人慢性不良反应相关。这项关联研究包括18名丹参酮诱导的cADRs患者、67名丹参酮耐受志愿者和两个由10,689和169,995名健康受试者组成的普通人群数据库。与一般对照组(OR = 6.25，Pc = 7.20 × 10−5；OR = 7.14，Pc = 8.00 × 10−6)和耐受组(OR = 5.09，Pc = 10−6)相比，丹参酮诱导的cADRS患者携带HLAA*02：01的频率显著增加(OR = 6.25，Pc = 7.20 × 10−5；OR = 7.14，Pc = 8.00× 10−6)。分子对接实验证实丹参酮成分对≤−-A*02：01(HLA7.5kcal/ )具有较高的亲和力。提示人类白细胞抗原-A*02：01可作为丹参酮个体化治疗的有前景的预测指标。
Tanshinone, a widely used Chinese patent medicine, has been confirmed to have various kinds of pharmacological effects although frequently causing cutaneous adverse drug reactions (cADRs). We aim to identify whether human leukocyte antigen (HLA) class I alleles are associated with tanshinone-induced cADRs in Han Chinese. The association study including 18 patients with tanshinone-induced cADRs, 67 tanshinone-tolerant volunteers, and two general population databases consisted of 10,689 and 169,995 healthy subjects was performed. The frequency of tanshinone-induced cADRs patients carryingHLA-A*02:01was significantly higher when compared with the general control groups (OR = 6.25, Pc = 7.20 × 10−5; OR = 7.14, Pc = 8.00 × 10−6), and with the tolerant group (OR = 5.09, Pc = 0.024). The molecular docking assay confirmed high affinity of the ingredients of tanshinone towardsHLA-A*02:01(≤−7.5 kcal/mol). The result suggestedHLA-A*02:01may work as a promisingly predictive marker for tanshinone personalized therapy in Han Chinese.