title: HLA Allele Frequencies in 5802 Koreans: Varied Allele Types Associated with SJS/TEN According to Culprit Drugs.
abstract: OBJECTIVE
  Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are very serious forms of drug-induced cutaneous adverse reaction. SJS/TEN induced by certain drug is well known to be associated with some human leukocyte antigen (HLA) gene type. We aimed to explore HLA allele frequencies and their association with SJS/TEN according to culprit drugs in Korea.
  
  
  METHODS
  We enrolled 5802 subjects who had results of HLA typing test from August 2005 to July 2014. Total 28 SJS/TEN patients were categorized based on culprit drugs (allopurinol, lamotrigine, carbamazepine) and identified the presence of HLA-B*58:01, HLA-B*44:03, HLA-B*15:02, and HLA-A*31:01.
  
  
  RESULTS
  HLA-A*24:02 (20.5%), HLA-B*44:03 (10.0%), and HLA-Cw*01:02 (17.1%) were the most frequent type in HLA-A, -B, and -C genes, respectively. Allele frequencies of HLA-B*58:01, HLA-B*44:03, HLA-A*31:01, and HLA-B*15:02 were 7.0%, 10.0%, 5.0%, and 0.3%, respectively. In 958 allopurinol users, 9 subjects (0.9%) were diagnosed with SJS/TEN. Among them, 8 subjects possessed HLA-B*58:01 allele. SJS/TEN induced by allopurinol was more frequently developed in subjects with HLA-B*58:01 than in subjects without it [odds ratio: 57.4; confidence interval (CI) 7.12-463.50; p<0.001]. Allopurinol treatment, based on screening by HLA-B*58:01 genotyping, could be more cost-effective than that not based on screening. HLA-B*44:03 may be associated with lamotrigine-induced SJS/TEN (odds ratio: 12.75; CI 1.03-157.14; p=0.053). Among carbamazepine users, only two patients experienced SJS/TEN and possessed neither HLA-B*15:02 nor HLA-A*31:03.
  
  
  CONCLUSIONS
  HLA gene frequencies varied in Korea. Screening of HLA-B*58:01 before the use of allopurinol might be needed to anticipate probability of SJS/TEN.
authors.affiliation: Division of Allergy and Immunology, Department of Internal Medicine, Institute of Allergy, Yonsei University College of Medicine, Seoul, Korea.
authors.forename: Hye Jung
authors.initials: HJ
authors.lastname: Park
authors.affiliation: Division of Allergy and Immunology, Department of Internal Medicine, Institute of Allergy, Yonsei University College of Medicine, Seoul, Korea.
authors.forename: Young Joo
authors.initials: YJ
authors.lastname: Kim
authors.affiliation: Division of Allergy and Immunology, Department of Internal Medicine, Institute of Allergy, Yonsei University College of Medicine, Seoul, Korea.
authors.forename: Dong Hyun
authors.initials: DH
authors.lastname: Kim
authors.affiliation: Division of Allergy and Immunology, Department of Internal Medicine, Institute of Allergy, Yonsei University College of Medicine, Seoul, Korea.
authors.forename: Junho
authors.initials: J
authors.lastname: Kim
authors.affiliation: Division of Allergy and Immunology, Department of Internal Medicine, Institute of Allergy, Yonsei University College of Medicine, Seoul, Korea.
authors.forename: Kyung Hee
authors.initials: KH
authors.lastname: Park
authors.affiliation: Division of Allergy and Immunology, Department of Internal Medicine, Institute of Allergy, Yonsei University College of Medicine, Seoul, Korea.
authors.forename: Jung Won
authors.initials: JW
authors.lastname: Park
authors.affiliation: Division of Allergy and Immunology, Department of Internal Medicine, Institute of Allergy, Yonsei University College of Medicine, Seoul, Korea. jhleemd@yuhs.ac.
authors.forename: Jae Hyun
authors.initials: JH
authors.lastname: Lee
mesh_terms: D000328:Adult; D000368:Aged; D000483:Alleles; D000493:Allopurinol / Q000009:adverse effects / Q000494:pharmacology*; D000927:Anticonvulsants / Q000009:adverse effects*; D044466:Asian People / Q000235:genetics*; D002220:Carbamazepine / Q000009:adverse effects / Q000494:pharmacology*; D016022:Case-Control Studies; D064420:Drug-Related Side Effects and Adverse Reactions / Q000235:genetics* / Q000276:immunology; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D015235:HLA-B Antigens / Q000235:genetics*; D006801:Humans; D000077213:Lamotrigine; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D020641:Polymorphism, Single Nucleotide; D056910:Republic of Korea; D012189:Retrospective Studies; D012307:Risk Factors; D013262:Stevens-Johnson Syndrome / Q000208:ethnology / Q000209:etiology / Q000235:genetics*; D014227:Triazines / Q000009:adverse effects / Q000494:pharmacology*
chemical_list: D000927:Anticonvulsants; D015235:HLA-B Antigens; D014227:Triazines; D002220:Carbamazepine; D000493:Allopurinol; D000077213:Lamotrigine
keywords: Allopurinol; HLA-B*58:01; Stevens-Johnson syndrome; human leukocyte antigen; toxic epidermal necrolysis