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 carrying HLA-A*02:01 was 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 towards HLA-A*02:01 (≤−7.5 kcal/mol). The result suggested HLA-A*02:01 may work as a promisingly predictive marker for tanshinone personalized therapy in Han Chinese.
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This work was supported by the National Natural Science Foundation of China (31371274, 81472873, and 81872525), the National Key Research and Development Program (2016YFC0905001) and the Shanghai Municipal Commission of Science and Technology Program (14DJ1400100), Natural Science Foundation of Henan Province (No. 182300410010), Scientific and Technological Research in Open Collaborative Projects of Henan Province (152106000044). The authors wish to acknowledge the department of dermatology (Huashan Hospital [Shanghai, China], Fudan University [Shanghai, China]) for their assistance in this article and the Department of Cardiology (the First Affiliated Hospital of Zhengzhou University [Zhengzhou, China]) for offering clinical data.
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Zhu, Q., Zhang, Y., Xuan, J. et al. HLA-A*02:01 allele is associated with tanshinone-induced cutaneous drug reactions in Chinese population. Pharmacogenomics J (2019) doi:10.1038/s41397-019-0121-1