Abstract
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.
This is a preview of subscription content, access via your institution
Access options
Subscribe to this journal
Receive 6 print issues and online access
$259.00 per year
only $43.17 per issue
Buy this article
- Purchase on Springer Link
- Instant access to full article PDF
Prices may be subject to local taxes which are calculated during checkout
Similar content being viewed by others
References
Zhou L, Zuo Z, Chow MS. Danshen: an overview of its chemistry, pharmacology, pharmacokinetics, and clinical use. J Clin Pharmacol. 2005;45:1345–9.
Zhang Y, Jiang P, Ye M, Kim SH, Jiang C, Lü J. Tanshinones: sources, pharmacokinetics and anti-cancer activities. Int J Mol Sci. 2012;13:13621–66.
Hao YF, Jiang JG. Origin and evolution of China Pharmacopoeia and its implication for traditional medicines. Mini Rev Med Chem. 2015;15:595–603.
Chinese PC. Pharmacopoeia of People’s Republic of China. I. Beijing: China Medical Science Press; 2010.
Cheng TO. Cardiovascular effects of Danshen. Int J Cardiol. 2007;121:9–22.
Lee JH, Shin YJ, Kim HJ, Oh JH, Jang YP, Lee YJ. Danshen extract does not alter pharmacokinetics of docetaxel and clopidogrel, reflecting its negligible potential in P-glycoprotein- and cytochrome P4503A-mediated herb-drug interactions. Int J Pharm. 2011;410:68–74.
Cho YH, Ku CR, Hong ZY, Heo JH, Kim EH, Choi DH, et al. Therapeutic effects of water soluble danshen extracts on atherosclerosis. Evid Based Complement Altern Med. 2013;2013:623639.
Hügel HM, Jackson N. Danshen diversity defeating dementia. Bioorg Med Chem Lett. 2014;24:708–16.
Maione F, Mascolo N. Danshen and the cardiovascular system: new advances for an old remedy. Semin Thromb Hemost. 2016;42:321–2.
Wang X, Morris-Natschke SL, Lee KH. New developments in the chemistry and biology of the bioactive constituents of Tanshen. Med Res Rev. 2007;27:133–48.
Gu M, Zhang G, Su Z, Ouyang F. Identification of major active constituents in the fingerprint of Salvia miltiorrhiza Bunge developed by high-speed counter-current chromatography. J Chromatogr A. 2004;1041:239–43.
Fang X, Wang J, Zhang S, Zhao Q, Zheng Z, Song Z. Simultaneous extraction of hydrosoluble phenolic acids and liposoluble tanshinones from Salviae miltiorrhizae radix by an optimized microwave-assisted extraction method. Sep Purif Technol. 2012;86:149–56.
Cha JD, Lee JH, Choi KM, Choi SM, Park JH. Synergistic effect between cryptotanshinone and antibiotics against clinic methicillin and vancomycin-resistant staphylococcus aureus. Evid Based Complement Altern Med. 2014;2014:450572.
Chen W, Lu Y, Chen G, Huang S. Molecular evidence of cryptotanshinone for treatment and prevention of human cancer. Anticancer Agents Med Chem. 2013;13:979–87.
Fang J, Little PJ, Xu S. Atheroprotective effects and molecular targets of tanshinones derived from herbal medicine danshen. Med Res Rev. 2018;38:201–28.
Maione F, Cantone V, Chini MG, De Feo V, Mascolo N, Bifulco G. Molecular mechanism of tanshinone IIA and cryptotanshinone in platelet anti-aggregating effects: an integrated study of pharmacology and computational analysis. Fitoterapia. 2015;100:174–8.
Song M, Hang TJ, Zhang Z, Chen HY. Effects of the coexisting diterpenoid tanshinones on the pharmacokinetics of cryptotanshinone and tanshinone IIA in rat. Eur J Pharm Sci. 2007;32:247–53.
Song M, Hang TJ, Zhang ZX, Du R, Chen J. Determination of cryptotanshinone and its metabolite in rat plasma by liquid chromatography-tandem mass spectrometry. J Chromatogr B Anal Technol Biomed Life Sci. 2005;827:205–9.
Huang HY, Luo XQ, Chan LS, Cao ZH, Sun XF, Xu JH. Cutaneous adverse drug reactions in a hospital-based Chinese population. Clin Exp Dermatol. 2011;36:135–41.
Li LF, Ma C. Epidemiological study of severe cutaneous adverse drug reactions in a city district of China. Clin Exp Dermatol. 2006;31:642–7.
Lim YL, Thirumoorthy T. Serious cutaneous adverse reactions to traditional Chinese medicines. Singap Med J. 2005;46:714–7.
Fu X, Yang F, Zhu Q, Luo X. Clinical review of 922 inpatients with drug eruptions. Chin J Dermatol. 2015;48:12.
Goncalo M, Coutinho I, Teixeira V, Gameiro AR, Brites MM, Nunes R, et al. HLA-B*58:01 is a risk factor for allopurinol-induced DRESS and Stevens-Johnson syndrome/toxic epidermal necrolysis in a Portuguese population. Br J Dermatol. 2013;169:660–5.
Zhang Y, Wang J, Zhao L-M, Peng W, Shen G-Q, Xue L, et al. Strong association between HLA-B*1502 and carbamazepine-induced Stevens-Johnson syndrome and toxic epidermal necrolysis in mainland Han Chinese patients. Eur J Clin Pharmacol. 2011;67:885–7.
Bharadwaj M, Illing P, Theodossis A, Purcell AW, Rossjohn J, McCluskey J. Drug hypersensitivity and human leukocyte antigens of the major histocompatibility complex. Annu Rev Pharm Toxicol. 2012;52:401–31.
Sousa-Pinto B, Pinto-Ramos J, Correia C, Gonçalves-Costa G, Gomes L, Gil-Mata S, et al. Pharmacogenetics of abacavir hypersensitivity: a systematic review and meta-analysis of the association with HLA-B*57:01. J Allergy Clin Immunol. 2015;136:1092–4.
Zhou F, Cao H, Zuo X, Zhang T, Zhang X, Liu X, et al. Deep sequencing of the MHC region in the Chinese population contributes to studies of complex disease. Nat Genet. 2016;48:740–6.
Zhou XY, Zhu FM, Li JP, Mao W, Zhang DM, Liu ML, et al. High-resolution analyses of human leukocyte antigens allele and haplotype frequencies based on 169,995 volunteers from the China Bone Marrow Donor Registry Program. PLoS ONE. 2015;10:e0139485.
Haldane JB. The estimation and significance of the logarithm of a ratio of frequencies. Ann Hum Genet. 1956;20:309–11.
Hanley JA, McNeil BJ. The meaning and use of the area under a receiver operating characteristic (ROC) curve. Radiology. 1982;143:29–36.
Wang S, Liu L, Zhao Z, Wen W, Li R, Tu P. Clinical analysis of cutaneous adverse drug reactions: a 15-year retrospective survey of 360 inpatients. J Dermatol. 2014;41(Suppl. 1):77.
Zeng ZP, Jiang JG. Analysis of the adverse reactions induced by natural product-derived drugs. Br J Pharmacol. 2010;159:1374–91.
Chan K, Zhang H, Lin ZX. An overview on adverse drug reactions to traditional Chinese medicines. Br J Clin Pharmacol. 2015;80:834–43.
Teng L, Zu Q, Li G, Yu T, Job KM, Yang X, et al. Herbal medicines: challenges in the modern world. Part 3. China Jpn Expert Rev Clin Pharmacol. 2016;9:1225–33.
Job KM, Kiang TK, Constance JE, Sherwin CM, Enioutina EY. Herbal medicines: challenges in the modern world. Part 4. Canada and United States. Expert Rev Clin Pharmacol. 2016;9:1597–609.
Sammons HM, Gubarev MI, Krepkova LV, Bortnikova VV, Corrick F, Job KM, et al. Herbal medicines: challenges in the modern world. Part 2. European Union and Russia. Expert Rev Clin Pharmacol. 2016;9:1117–27.
Lucena MI, Molokhia M, Shen Y, Urban TJ, Aithal GP, Andrade RJ, et al. Susceptibility to amoxicillin-clavulanate-induced liver injury is influenced by multiple HLA class I and II alleles. Gastroenterology. 2011;141:338–47.
Fricke-Galindo I, Martínez-Juárez IE, Monroy-Jaramillo N, Jung-Cook H, Falfán-Valencia R, Ortega-Vázquez A, et al. HLA-A*02:01:01/-B*35:01:01/-C*04:01:01 haplotype associated with lamotrigine-induced maculopapular exanthema in Mexican Mestizo patients. Pharmacogenomics. 2014;15:1881–91.
Qiu F, Jiang J, Ma Y, Wang G, Gao C, Zhang X, et al. Opposite effects of single-dose and multidose administration of the ethanol extract of danshen on CYP3A in healthy volunteers. Evid Based Complement Altern Med. 2013;2013:730734.
Padovan E, Mauri-Hellweg D, Pichler WJ, Weltzien HU. T cell recognition of penicillin G: structural features determining antigenic specificity. Eur J Immunol. 1996;26:42–8.
Sullivan JR, Shear NH. The drug hypersensitivity syndrome: what is the pathogenesis? Arch Dermatol. 2001;137:357–64.
Faul F, Erdfelder E, Lang AG, Buchner A. G*Power 3: a flexible statistical power analysis program for the social, behavioral, and biomedical sciences. Behav Res Methods. 2007;39:175–91.
Acknowledgements
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.
Author information
Authors and Affiliations
Corresponding authors
Ethics declarations
Conflict of interest
The authors declare that they have no conflict of interest.
Additional information
Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Rights and permissions
About this article
Cite this article
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 20, 408–414 (2020). https://doi.org/10.1038/s41397-019-0121-1
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1038/s41397-019-0121-1