title: 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.
  
  
  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*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).
  
  
  CONCLUSIONS
  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.
authors.affiliation: aInstitutes of Biomedical Sciences bDepartment of Dermatology, Huashan Hospital cChildren's Hospital and Institutes of Biomedical Sciences, Fudan University, Shanghai dDepartment of Pharmacology, School of Medicine, Zhengzhou University, Zhengzhou, China.
authors.forename: Sijia
authors.initials: S
authors.lastname: Yan
authors.forename: Sheng-An
authors.initials: SA
authors.lastname: Chen
authors.forename: Wen
authors.initials: W
authors.lastname: Zhang
authors.forename: Fanping
authors.initials: F
authors.lastname: Yang
authors.forename: Ying
authors.initials: Y
authors.lastname: Yang
authors.forename: Qinyuan
authors.initials: Q
authors.lastname: Zhu
authors.forename: Huizhong
authors.initials: H
authors.lastname: Zhu
authors.forename: Xinfen
authors.initials: X
authors.lastname: Sun
authors.forename: Menglin
authors.initials: M
authors.lastname: Jiang
authors.forename: Yu
authors.initials: Y
authors.lastname: Su
authors.forename: Lirong
authors.initials: L
authors.lastname: Zhang
authors.forename: Qinghe
authors.initials: Q
authors.lastname: Xing
authors.forename: Xiaoqun
authors.initials: X
authors.lastname: Luo
mesh_terms: D000328:Adult; D044466:Asian People / Q000208:ethnology / Q000235:genetics*; D002681:China / Q000208:ethnology; D005076:Exanthema / Q000139:chemically induced / Q000235:genetics*; D005260:Female; D056726:Genetic Association Studies; D015234:HLA-A Antigens / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D013743:Tetanus Antitoxin / Q000633:toxicity*
chemical_list: D015234:HLA-A Antigens; D013743:Tetanus Antitoxin