title: Strong association between HLA-B*5801 and allopurinol-induced Stevens-Johnson syndrome and toxic epidermal necrolysis in a Thai population.
abstract: OBJECTIVE
  Allopurinol, a uric acid lowering drug commonly used for hyperuricemia and gouty arthritis, has been reported as a common cause of severe cutaneous adverse drug reactions (SCAR) including Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN). A strong association between allopurinol-induced SCAR and HLA-B*5801 was observed in a Han Chinese population with high frequency of this allele, whereas only a moderate association was observed in populations with low frequency (i.e. European and Japanese). This study investigated the relationship between SJS/TEN and HLA-B*5801 in a Thai population that has a high allelic frequency of this allele.
  
  
  METHODS
  Twenty-seven allopurinol-induced SJS/TEN and 54 allopurinol-tolerant patients were enrolled in the study. The presence of HLA-B*5801 and HLA-B genotypes in these patients were analyzed using a PG5801 DNA detection kit and sequence-based typing, respectively.
  
  
  RESULTS
  All of the 27 (100%) allopurinol-induced SJS/TEN patients who were examined carried HLA-B*5801 whereas only seven (12.96%) of the control patients had this allele. The risk of allopurinol-induced SJS/TEN was significantly greater in patients with HLA-B*5801 when compared with those who did not carry this allele, with an odds ratio of 348.3 (95% confidence interval=19.2-6336.9, P = 1.6 x10). The sensitivity and specificity of the HLA-B*5801 allele for prediction of allopurinol-induced SJS/TEN were 100 and 87%, respectively. By assuming a 0.2% prevalence rate, the positive predictive value and the negative predictive value of the HLA-B*5801 allele was 1.52 and 100%, respectively.
  
  
  CONCLUSIONS
  A strong association of allopurinol-induced SJS/TEN with the HLA-B*5801 allele was observed in a Thai population. The results suggest that HLA-B*5801 is a valid genetic marker for screening Thai individuals who may be at risk for allopurinol-induced life-threatening SJS and TEN.
authors.affiliation: Departments of Pharmacology, Khon Kaen University, Khon Kaen, Thailand. wichitt@kku.ac.th
authors.forename: Wichittra
authors.initials: W
authors.lastname: Tassaneeyakul
authors.forename: Thawinee
authors.initials: T
authors.lastname: Jantararoungtong
authors.forename: Pei
authors.initials: P
authors.lastname: Chen
authors.forename: Pao-Yu
authors.initials: PY
authors.lastname: Lin
authors.forename: Somsak
authors.initials: S
authors.lastname: Tiamkao
authors.forename: Usanee
authors.initials: U
authors.lastname: Khunarkornsiri
authors.forename: Pachadaporn
authors.initials: P
authors.lastname: Chucherd
authors.forename: Parinya
authors.initials: P
authors.lastname: Konyoung
authors.forename: Suda
authors.initials: S
authors.lastname: Vannaprasaht
authors.forename: Charoen
authors.initials: C
authors.lastname: Choonhakarn
authors.forename: Pornrith
authors.initials: P
authors.lastname: Pisuttimarn
authors.forename: Alisara
authors.initials: A
authors.lastname: Sangviroon
authors.forename: Wongwiwat
authors.initials: W
authors.lastname: Tassaneeyakul
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000493:Allopurinol / Q000009:adverse effects*; D016022:Case-Control Studies; D003430:Cross-Sectional Studies; D005260:Female; D005787:Gene Frequency; D005819:Genetic Markers; D005838:Genotype; D006074:Gout Suppressants / Q000009:adverse effects*; D015235:HLA-B Antigens / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D013262:Stevens-Johnson Syndrome / Q000139:chemically induced* / Q000208:ethnology / Q000209:etiology / Q000235:genetics*; D013785:Thailand / Q000208:ethnology
chemical_list: D005819:Genetic Markers; D006074:Gout Suppressants; D015235:HLA-B Antigens; C500126:HLA-B*58:01 antigen; D000493:Allopurinol