title: HLA-B*5901 is strongly associated with methazolamide-induced Stevens-Johnson syndrome/toxic epidermal necrolysis.
abstract: OBJECTIVE
  The carbonic anhydrase inhibitor methazolamide infrequently causes Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN). An association between these diseases and the HLA-B59 serotype has been suggested in case reports. This study examined the disease-associated B*59 allele and investigated the association of these diseases with other HLA class I alleles.
  
  
  METHODS
  We performed high-resolution HLA-A, -B and -C genotyping in five patients with methazolamide-induced SJS/TEN using a PCR-sequencing-based typing method and analyzed the association between HLA-class I alleles and occurrence of methazolamide-induced SJS/TEN.
  
  
  RESULTS
  B*5901 and Cw*0102 alleles were observed in all patients and A*2402 was observed in four patients. The B*5901 allele showed the strongest association with methazolamide-induced SJS/TEN (p < 0.001; odds ratio: 249.8; 95% CI: 13.4-4813.5), followed by Cw*0102 (p = 0.004; odds ratio: 22.1; 95% CI: 1.2-414.3), when compared with the general population as a control. The frequency of the patients carrying B*5901, Cw*0102 and A*2402 simultaneously was significantly higher than that in the general population (p < 0.001; odds ratio: 110.1; 95% CI: 11.7-1038.6).
  
  
  CONCLUSIONS
  A strong association was observed between HLA-B*5901 and methazolamide-induced SJS/TEN in Korean patients. HLA-B*5901 may be a useful screening marker for predicting methazolamide-induced SJS/TEN in patients of Korean and Japanese ancestry.
authors.affiliation: Department of Internal Medicine, Seoul National University College of Medicine, Seoul, South Korea.
authors.forename: Sae-Hoon
authors.initials: SH
authors.lastname: Kim
authors.forename: Myunghwa
authors.initials: M
authors.lastname: Kim
authors.forename: Kyung Wha
authors.initials: KW
authors.lastname: Lee
authors.forename: Sang-Heon
authors.initials: SH
authors.lastname: Kim
authors.forename: Hye-Ryun
authors.initials: HR
authors.lastname: Kang
authors.forename: Heung-Woo
authors.initials: HW
authors.lastname: Park
authors.forename: Young-Koo
authors.initials: YK
authors.lastname: Jee
mesh_terms: D000328:Adult; D000483:Alleles; D005260:Female; D005838:Genotype; D015235:HLA-B Antigens / Q000235:genetics*; D006801:Humans; D008297:Male; D008704:Methazolamide / Q000009:adverse effects* / Q000627:therapeutic use; D008875:Middle Aged; D056910:Republic of Korea; D013262:Stevens-Johnson Syndrome / Q000139:chemically induced / Q000209:etiology / Q000235:genetics* / Q000276:immunology
chemical_list: D015235:HLA-B Antigens; D008704:Methazolamide