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Objective:Tanshinone are a class of abietane diterpene compound isolated from Danshen,a well-known herb in Traditional Chinese Medicine(TCM).The commercially available tanshinone preparation serves as an alternative,effective and cheap antimicrobial for the treatment of infections in China.However,it also frequently causes cutaneous adverse drug reactions(cADRs).Since allotypes of human leukocyte antigens(HLA)gene were suggested to implicate in drug induced hypersensitivity,this study aims to assess if there is association between tanshinone-induced cADRs and HLA class I alleles in Chinese Han population.Docking simulations was tried to target the causative component of tanshinone.Subjects and Methods:We performed an association study of 18 subjects with tanshinone-induced cADRs,67 tanshinone-tolerant patients,and 283 general subjects from the human MHC database,all of whom are Han Chinese.HLA-A,-B and –C genotyping were performed and computational analyses were done.Results:The frequencies of the tanshinone-induced cADRs patients carrying HLA-A*02:01 and HLA-C*01:02 were 50.00%(9/18)and 61.11%(11/18),significantly higher compared to general Chinese Han population(10.60%,30/283,OR=8.43; Pc = 8.03x10-6 ;33.57%,95/283,OR=3.11; Pc = 0.018),or to tanshinone tolerant patients(16.41%,11/67,OR=5.09; Pc =0.008 ;31.34%,21/67,OR=3.44; Pc = 0.021).The logistic regression suggested that both these two alleles could be considered as individual risk factors when compared with the control groups(HLA-A*02:01:Pc=1.38x10-5,OR=10.23,Pc=0.003,OR=6.47; HLA-C*01:02:Pc=0.009,OR=4.03,Pc=0.015,OR=4.45).The docking scores towards HLA-A*02:01(<-8.0 kcal/mol)were low and even lower towards HLA-C*01:02(<-9.0 kcal/mol).Among them,cryptotanshinone shared similar hydrogen bonds with other components when docked into the cavity of HLA-A*02:01 and HLA-C*01:02 as well.Conclusion:This study provided a comprehensive and systematic analysis of HLA alleles associated with tanshinone-cADRs in Chinese population and the HLA-A*02:01 and HLA-C*01:02 maybe work as promising markers for tanshinone personalized therapy,which could lead to safer tanshinone prescribing and less cutaneous adverse events.