title: Candidate HLA genes for prediction of co-trimoxazole-induced severe cutaneous reactions.
abstract: BACKGROUND
  Co-trimoxazole is a sulfonamide-containing antibiotic that is effective in the treatment of several infections and for prophylaxis of Pneumocystis jiroveci pneumonia. This drug has been reported as a common culprit drug for the Stevens-Johnson syndrome (SJS) and for toxic epidermal necrolysis (TEN). Human leukocyte antigens (HLAs) play a key role in the immunopathogenesis of severe cutaneous reactions induced by several drugs. This study investigated the association between the HLA class I and HLA-DRB1 polymorphisms and co-trimoxazole-induced SJS/TEN in a Thai population.
  
  
  METHODS
  Forty-three patients with co-trimoxazole-induced SJS/TEN and 91 co-trimoxazole-tolerant patients were enrolled in the study. HLA class I and HLA-DRB1 were genotyped using the reverse sequence-specific oligonucleotide probe method.
  
  
  RESULTS
  The frequencies of three alleles of HLA, namely HLA-B*15:02, HLA-C*06:02, and HLA-C*08:01, were significantly higher in the co-trimoxazole-induced SJS/TEN group compared with controls. The risks for co-trimoxazole-induced SJS/TEN in patients with the HLA-B*15:02, HLA-C*06:02, or HLA-C*08:01 allele were about 3-11-fold higher when compared with those who did not carry one of these alleles. Individuals who carried the HLA-B*15:02-C*08:01 haplotype had a 14-fold higher risk for co-trimoxazole-induced SJS/TEN.
  
  
  CONCLUSIONS
  Evidence of associations between co-trimoxazole-induced SJS/TEN and HLA alleles including HLA-B*15:02, HLA-C*06:02, and HLA-C*08:01 were found in the study population. These findings may suggest that apart from the HLA molecules, other molecules involved in the molecular pathogenesis of these severe cutaneous adverse drug reactions may play an important role in the susceptibility of individuals to SJS/TEN caused by co-trimoxazole.
authors.affiliation: aDepartment of Pharmacology bPharmacy Unit cDepartment of Medicine, Faculty of Medicine dFaculty of Pharmaceutical Sciences, Khon Kaen University, Khon Kaen eMedical Genetics Center, Medical Life Science Institute, Department of Medical Sciences, Ministry of Public Health fHealth Product Vigilance Center, Food and Drug Administration, Ministry of Public Health, Nonthaburi gPharmacy Unit hDepartment of Medicine, Udon Thani Hospital, Udon Thani iBuddhachinaraj Hospital, Phitsanulok jLampang Hospital, Lampang kRayong Hospital, Rayong lSongkhla Hospital, Songkhla mChiangraiprachanukroh Hospital, Chiangrai, Thailand.
authors.forename: Thachanan
authors.initials: T
authors.lastname: Kongpan
authors.forename: Surakameth
authors.initials: S
authors.lastname: Mahasirimongkol
authors.forename: Parinya
authors.initials: P
authors.lastname: Konyoung
authors.forename: Sirimas
authors.initials: S
authors.lastname: Kanjanawart
authors.forename: Pansu
authors.initials: P
authors.lastname: Chumworathayi
authors.forename: Nuanjun
authors.initials: N
authors.lastname: Wichukchinda
authors.forename: Runglak
authors.initials: R
authors.lastname: Kidkeukarun
authors.forename: Suphanlinee
authors.initials: S
authors.lastname: Preechakul
authors.forename: Usanee
authors.initials: U
authors.lastname: Khunarkornsiri
authors.forename: Warawut
authors.initials: W
authors.lastname: Bamrungram
authors.forename: Butsaban
authors.initials: B
authors.lastname: Supharatwattanakun
authors.forename: Piroon
authors.initials: P
authors.lastname: Mootsikapun
authors.forename: Supanida
authors.initials: S
authors.lastname: Kwangsukstid
authors.forename: Sukanda
authors.initials: S
authors.lastname: Denjanta
authors.forename: Suda
authors.initials: S
authors.lastname: Vannaprasaht
authors.forename: Watcharee
authors.initials: W
authors.lastname: Rungapiromnan
authors.forename: Wimon
authors.initials: W
authors.lastname: Suwankesawong
authors.forename: Wongwiwat
authors.initials: W
authors.lastname: Tassaneeyakul
authors.forename: Wichittra
authors.initials: W
authors.lastname: Tassaneeyakul
mesh_terms: D000328:Adult; D000483:Alleles; D003710:Demography; D005260:Female; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D006680:HLA Antigens / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D013262:Stevens-Johnson Syndrome / Q000235:genetics*; D015662:Trimethoprim, Sulfamethoxazole Drug Combination / Q000009:adverse effects*
chemical_list: D006680:HLA Antigens; D015662:Trimethoprim, Sulfamethoxazole Drug Combination