The majority of patients who experience cutaneous adverse drug reactions(cADRs)concurrently receive multiple medications,meaning that the causative drug remains unidentified.We explored the association between human l...The majority of patients who experience cutaneous adverse drug reactions(cADRs)concurrently receive multiple medications,meaning that the causative drug remains unidentified.We explored the association between human leukocyte antigen(HLA)alleles and cADRs,regardless of the allergenic drug,to investigate whether different drug-induced cADRs were associated with the same or similar risk alleles in a Han Chinese population.We genotyped a sample of 146 cADR patients and 230 population controls from the same hospital and systematically analyzed the association between HLA Class I genes and cADRs.The carrier frequency of HLAB∗46:01 in cADR patients was found to be significantly higher than that in population controls(P=.0021,odds ratio[OR]=2.18,95%confidence interval[CI]:1.33-2.58).Subgroup analysis showed that HLA-B∗46:01 was significantly associated with urticaria and erythema multiforme(P=.0077,OR=2.53,95%CI:1.30-4.91;and P=.0049,OR=2.77,95%CI:1.39-5.50,respectively).Furthermore,a significant association was also detected between HLA-A∗02:01 and erythema multiforme(P=.0038,OR=2.65,95%CI:1.31-5.33).This study is the first to demonstrate that HLA-B∗46:01 is a risk allele for cADRs in a Han Chinese population,indicating that screening for HLA-B∗46:01 prior to the administration of medication may predict the risk of developing cADRs.展开更多
Abacavir is an effective nucleoside analog reverse transcriptase inhibitor used to treat human immunodeficiency virus(HIV) infected patients.Its main side effect is hypersensitivity reaction(HSR).The incidence of the ...Abacavir is an effective nucleoside analog reverse transcriptase inhibitor used to treat human immunodeficiency virus(HIV) infected patients.Its main side effect is hypersensitivity reaction(HSR).The incidence of the HSR is associated with ethnicity among patients exposed to abacavir,and retrospective and prospective studies show a significantly increased risk of abacavir-induced HSR in human leukocyte antigen(HLA)-B*57:01-carrying patients.Immunological studies indicated that abacavir interacts specifically with HLA-B*57:01 and changed the binding specificity between the HLA molecule and the HLA-presented endogenous peptide repertoire,leading to a systemic autoimmune reaction.HLA-B*57:01 screening,combined with patch testing,had clinically predictive value and cost-effective impact in reducing the incidence of abacavir-induced HSR regardless of the HLA-B*57:01 prevalence in the population.Therefore,the US Food and Drug Administration(FDA) and international HIV treatment guidelines recommend a routine HLA-B*57:01 screening prior to abacavir treatment to decrease false positive diagnosis and prevent abacavir-induced HSR.The studies of abacavir-induced HSR and the implementation of the HLA-B*57:01 screening in the clinic represent a successful example of the use of pharmacogenetics for personalized diagnosis and therapy.展开更多
基金This study was supported in part by grants from the National Natural Science Foundation of China(No.81071287 and No.31371274)the National Key Research and Development Program(No.2016 YFC0905001)+1 种基金the Scientific and Technological Research in Open Collaborative Projects of Henan Province(No.152106000044)the Shanghai Municipal Commission of Science and Technology Program(No.14DJ1400100).
文摘The majority of patients who experience cutaneous adverse drug reactions(cADRs)concurrently receive multiple medications,meaning that the causative drug remains unidentified.We explored the association between human leukocyte antigen(HLA)alleles and cADRs,regardless of the allergenic drug,to investigate whether different drug-induced cADRs were associated with the same or similar risk alleles in a Han Chinese population.We genotyped a sample of 146 cADR patients and 230 population controls from the same hospital and systematically analyzed the association between HLA Class I genes and cADRs.The carrier frequency of HLAB∗46:01 in cADR patients was found to be significantly higher than that in population controls(P=.0021,odds ratio[OR]=2.18,95%confidence interval[CI]:1.33-2.58).Subgroup analysis showed that HLA-B∗46:01 was significantly associated with urticaria and erythema multiforme(P=.0077,OR=2.53,95%CI:1.30-4.91;and P=.0049,OR=2.77,95%CI:1.39-5.50,respectively).Furthermore,a significant association was also detected between HLA-A∗02:01 and erythema multiforme(P=.0038,OR=2.65,95%CI:1.31-5.33).This study is the first to demonstrate that HLA-B∗46:01 is a risk allele for cADRs in a Han Chinese population,indicating that screening for HLA-B∗46:01 prior to the administration of medication may predict the risk of developing cADRs.
文摘Abacavir is an effective nucleoside analog reverse transcriptase inhibitor used to treat human immunodeficiency virus(HIV) infected patients.Its main side effect is hypersensitivity reaction(HSR).The incidence of the HSR is associated with ethnicity among patients exposed to abacavir,and retrospective and prospective studies show a significantly increased risk of abacavir-induced HSR in human leukocyte antigen(HLA)-B*57:01-carrying patients.Immunological studies indicated that abacavir interacts specifically with HLA-B*57:01 and changed the binding specificity between the HLA molecule and the HLA-presented endogenous peptide repertoire,leading to a systemic autoimmune reaction.HLA-B*57:01 screening,combined with patch testing,had clinically predictive value and cost-effective impact in reducing the incidence of abacavir-induced HSR regardless of the HLA-B*57:01 prevalence in the population.Therefore,the US Food and Drug Administration(FDA) and international HIV treatment guidelines recommend a routine HLA-B*57:01 screening prior to abacavir treatment to decrease false positive diagnosis and prevent abacavir-induced HSR.The studies of abacavir-induced HSR and the implementation of the HLA-B*57:01 screening in the clinic represent a successful example of the use of pharmacogenetics for personalized diagnosis and therapy.
