title: Genetic predictors of Stevens-Johnson syndrome and toxic epidermal necrolysis induced by aromatic antiepileptic drugs among the Chinese Han population.
abstract: BACKGROUND
  Previous studies suggested that one or more HLA alleles participate in the pathogenesis of AED-induced SJS/TEN, but most of these studies focused only on the HLA-B alleles.
  
  
  OBJECTIVE
  The aim of this study was to investigate the pathogenesis of AED-induced SJS/TEN across a broader spectrum of HLA alleles, including the HLA-A, -B and -DRB1 alleles, to further explore the association between each HLA allele and SJS/TEN induced by aromatic AEDs.
  
  
  METHODS
  A total of 27 patients exhibiting AED-induced SJS/TEN (16 CBZ-SJS/TEN, seven LTG-SJS/TEN, two PHT-SJS/TEN, and two PB-SJS/TEN patients) and 64 patients who exhibited tolerance to AEDs were recruited. High-resolution HLA genotyping was performed to estimate the prevalence of the HLA-A, -B and -DRB1 alleles for each subject.
  
  
  RESULTS
  Fifteen subjects in the SJS/TEN group (12 exhibiting CBZ-SJS/TEN, two exhibiting LTG-SJS, and one exhibiting PB-SJS) carried the HLA-B*15:02 allele, whereas only 4/64 subjects in the AED-tolerant group carried this allele; the carrier rate of HLA-B*15:02 was significantly different between the groups (P<0.001). Nine patients in the SJS/TEN group carried the HLA-DRB1*15:01 allele, while 12/64 subjects in the tolerant group carried this allele; considering that two patients in the SJS/TEN group (one exhibiting LTG-SJS and one exhibiting PB-SJS) were homozygous for this allele, the prevalence of HLA-DRB1*15:01 expression between the two groups was significantly different (P=0.041). Furthermore, the carrier rates of HLA-A*33:03, HLA-B*58:01, and HLA-DRB1*03:01 were lower in the SJS/TEN group compared with the AED-tolerant group. The carrier rates of these alleles between the two groups were significantly different (P=0.009, 0.016, and 0.009, respectively).
  
  
  CONCLUSIONS
  The HLA-DRB1*15:01 allele may represent a risk factor for AED-induced SJS/TEN among Han Chinese. The HLA-A*33:03, HLA-B*58:01, and HLA-DRB1*03:01 alleles may be "protectors" against AED-induced SJS/TEN, especially CBZ-SJS/TEN.
authors.affiliation: Department of Neurology, West China Hospital, Sichuan University, Chengdu, Sichuan Province, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Wang
authors.affiliation: Department of Neurology, West China Hospital, Sichuan University, Chengdu, Sichuan Province, China.
authors.forename: Fa-Yun
authors.initials: FY
authors.lastname: Hu
authors.affiliation: Department of Neurology, West China Hospital, Sichuan University, Chengdu, Sichuan Province, China.
authors.forename: Xin-Tong
authors.initials: XT
authors.lastname: Wu
authors.affiliation: Department of Neurology, West China Hospital, Sichuan University, Chengdu, Sichuan Province, China.
authors.forename: Dong-Mei
authors.initials: DM
authors.lastname: An
authors.affiliation: Department of Neurology, West China Hospital, Sichuan University, Chengdu, Sichuan Province, China.
authors.forename: Bo
authors.initials: B
authors.lastname: Yan
authors.affiliation: Department of Neurology, West China Hospital, Sichuan University, Chengdu, Sichuan Province, China. Electronic address: zhoudong66@yahoo.de.
authors.forename: Dong
authors.initials: D
authors.lastname: Zhou
mesh_terms: D000328:Adult; D000483:Alleles; D000927:Anticonvulsants / Q000009:adverse effects*; D044466:Asian People / Q000235:genetics; D004361:Drug Tolerance; D064420:Drug-Related Side Effects and Adverse Reactions / Q000235:genetics* / Q000276:immunology; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D015235:HLA-B Antigens / Q000235:genetics*; D059811:HLA-DRB1 Chains; D006801:Humans; D008297:Male; D008875:Middle Aged; D012307:Risk Factors; D013262:Stevens-Johnson Syndrome / Q000209:etiology* / Q000235:genetics* / Q000276:immunology / Q000473:pathology*
chemical_list: D000927:Anticonvulsants; D015235:HLA-B Antigens; D059811:HLA-DRB1 Chains; C553502:HLA-DRB1*03:01 antigen
keywords: Aromatic antiepileptic drugs; HLA-B*15:02 allele; HLA-DRB1*15:01 allele; Stevens–Johnson syndrome; Toxic epidermal necrolysis