HLA-A*02 alleles are associated with tetanus antitoxin-induced exanthematous drug eruptions in Chinese patients.

ABSTRACT

OBJECTIVE: Tetanus 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. PATIENTS AND METHODS: 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. RESULTS: 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*0201, HLA-A*0206, and HLA-A*0207, is significantly higher than that of the control group (OR=14.40; P=2.4×10). Furthermore, HLA-B*3901 was in complete linkage disequilibrium with HLA-A*0206 in the case patients. Consequently, the distribution of the HLA-A*0206/-B*3901 haplotype was also significantly different in the cases and the controls (OR=105.00; P=0.0024). CONCLUSION: The HLA-A*0206/-B*3901 haplotype is a potential genetic marker for the TAT-induced EDE. Furthermore, the HLA-A2 serotype, especially three alleles A*0201, A*0206, and A*0207, was identified to be associated with the TAT-induced EDE in the Han Chinese population for the first time.