title: HLA-B alleles associated with severe cutaneous reactions to antiepileptic drugs in Han Chinese.
abstract: OBJECTIVE
  HLA-B*15:02 screening is recommended before starting carbamazepine in Han Chinese and Southeast Asians because the allele is strongly predictive of Stevens-Johnson syndrome (SJS)/toxic epidermal necrolysis (TEN) induced by the drug. We examined whether other HLA-B alleles are also involved and whether the association extends to other antiepileptic drugs (AEDs).
  
  
  METHODS
  Cases of SJS/TEN induced by any AEDs were recruited and matched (1:5) with AED-tolerant controls. Carrier rates of HLA-B alleles, determined by direct sequencing, were compared between cases and controls. Results were meta-analyzed with previous studies to examine the associations between HLA-B*15:02 and SJS/TEN induced by phenytoin and lamotrigine.
  
  
  RESULTS
  A total of 55 cases (27 carbamazepine, 15 phenytoin, 6 lamotrigine, 7 other AEDs) and 275 controls were recruited. In drug-specific analysis, the carrier rate of HLA-B*15:02 was significantly higher in carbamazepine-SJS/TEN cases compared with carbamazepine-tolerant controls (92.3% vs. 11.9%; p = 3.51 × 10(-18) ; odds ratio (OR) 89.25; 95% confidence interval (CI) 19.25-413.83), and also in phenytoin-SJS/TEN cases compared with phenytoin-tolerant controls (46.7% vs. 20.0%; p = 0.045; OR 3.50; 95% CI 1.10-11.18). Meta-analyses showed a strong association of HLA-B*15:02 with phenytoin-SJS/TEN (p < 3 × 10(-4) ; OR 4.26; 95% CI 1.93-9.39) and, to a lesser extent, lamotrigine-SJS/TEN (p = 0.03; OR 3.59; 95% CI 1.15-11.22). Compared with drug-tolerant controls, the carrier rates of HLA-B*40:01 and HLA-B*58:01 were lower in cases of SJS/TEN induced by carbamazepine (p = 0.004) and other AEDs (p = 0.009), respectively.
  
  
  CONCLUSIONS
  SJS/TEN induced by carbamazepine and phenytoin is strongly and moderately associated with HLA-B*15:02 in Han Chinese, respectively. Possible protective associations with HLA-B*40:01 and HLA-B*58:01 warrant further investigation.
authors.affiliation: Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong, China.
authors.forename: Ying-Kit
authors.initials: YK
authors.lastname: Cheung
authors.forename: Suk-Hang
authors.initials: SH
authors.lastname: Cheng
authors.forename: Ernest J M
authors.initials: EJ
authors.lastname: Chan
authors.forename: Su V
authors.initials: SV
authors.lastname: Lo
authors.forename: Margaret H L
authors.initials: MH
authors.lastname: Ng
authors.forename: Patrick
authors.initials: P
authors.lastname: Kwan
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000927:Anticonvulsants / Q000009:adverse effects*; D044466:Asian People / Q000208:ethnology / Q000235:genetics; D016022:Case-Control Studies; D002648:Child; D004827:Epilepsy / Q000188:drug therapy / Q000235:genetics*; D005260:Female; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D015235:HLA-B Antigens / Q000235:genetics*; D006801:Humans; D008297:Male; D015201:Meta-Analysis as Topic; D008875:Middle Aged; D012189:Retrospective Studies; D012307:Risk Factors; D012871:Skin Diseases / Q000139:chemically induced* / Q000235:genetics*; D013262:Stevens-Johnson Syndrome / Q000139:chemically induced / Q000209:etiology / Q000235:genetics; D055815:Young Adult
chemical_list: D000927:Anticonvulsants; D015235:HLA-B Antigens
keywords: Antiepileptic drugs; Human leukocyte antigen; Pharmacogenetics; Stevens-Johnson syndrome; Toxic epidermal necrolysis