Sijia Yan, Sheng-An Chen, Wen Zhang, Fanping Yang, Ying Yang, Qinyuan Zhu, Huizhong Zhu, Xinfen Sun, Menglin Jiang, Yu Su, Lirong Zhang, Qinghe Xing, Xiaoqun Luo
Pharmacogenetics and genomics 2016 DecTetanus antitoxin (TAT) is an effective antitetanus medicine, but may sometimes cause adverse drug reactions such as rapid-onset anaphylactic shock and late-onset cutaneous adverse drug reactions, including exanthematous drug eruptions (EDE). Human leukocyte antigen (HLA) class I alleles are strongly associated with different types of cutaneous adverse drug reactions. This study aimed to assess whether there is an association between TAT-induced EDE and HLA-A, HLA-B, and HLA-C alleles in the Chinese Han population. We carried out an association study in 15 patients with TAT-induced EDE and two groups of general Han Chinese patients. Allele-level genotypes of the HLA-A, HLA-B, and HLA-C genes of each patient were determined using the PCR-sequence-specific oligonucleotides method. The carrier frequency of HLA serotype A2 was significantly higher in the TAT-induced EDE patients than in the general Han Chinese study participants from the human major histocompatibility complex database [n=283, odds ratio (OR)=6.93; P=0.0061]. Particularly, the carrier frequency of three A2 alleles, including HLA-A*02:01, HLA-A*02:06, and HLA-A*02:07, is significantly higher than that of the control group (OR=14.40; P=2.4×10). Furthermore, HLA-B*39:01 was in complete linkage disequilibrium with HLA-A*02:06 in the case patients. Consequently, the distribution of the HLA-A*02:06/-B*39:01 haplotype was also significantly different in the cases and the controls (OR=105.00; P=0.0024). The HLA-A*02:06/-B*39:01 haplotype is a potential genetic marker for the TAT-induced EDE. Furthermore, the HLA-A2 serotype, especially three alleles A*02:01, A*02:06, and A*02:07, was identified to be associated with the TAT-induced EDE in the Han Chinese population for the first time.
Sijia Yan, Sheng-An Chen, Wen Zhang, Fanping Yang, Ying Yang, Qinyuan Zhu, Huizhong Zhu, Xinfen Sun, Menglin Jiang, Yu Su, Lirong Zhang, Qinghe Xing, Xiaoqun Luo. HLA-A*02 alleles are associated with tetanus antitoxin-induced exanthematous drug eruptions in Chinese patients. Pharmacogenetics and genomics. 2016 Dec;26(12):538-546
PMID: 27749688
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