title: A whole-genome association study of major determinants for allopurinol-related Stevens-Johnson syndrome and toxic epidermal necrolysis in Japanese patients.
abstract: Stevens-Johnson syndrome and toxic epidermal necrolysis (SJS/TEN) are severe, cutaneous adverse drug reactions that are rare but life threatening. Genetic biomarkers for allopurinol-related SJS/TEN in Japanese were examined in a genome-wide association study in which Japanese patients (n=14) were compared with ethnically matched healthy controls (n=991). Associations between 890 321 single nucleotide polymorphisms and allopurinol-related SJS/TEN were analyzed by the Fisher's exact test (dominant genotype mode). A total of 21 polymorphisms on chromosome 6 were significantly associated with allopurinol-related SJS/TEN. The strongest association was found at rs2734583 in BAT1, rs3094011 in HCP5 and GA005234 in MICC (P=2.44 × 10(-8); odds ratio=66.8; 95% confidence interval, 19.8-225.0). rs9263726 in PSORS1C1, also significantly associated with allopurinol-related SJS/TEN, is in absolute linkage disequilibrium with human leukocyte antigen-B*5801, which is in strong association with allopurinol-induced SJS/TEN. The ease of typing rs9263726 makes it a useful biomarker for allopurinol-related SJS/TEN in Japanese.
authors.affiliation: Department of Medicinal Safety Science, National Institute of Health Sciences, Tokyo, Japan. tohkin@phar.nagoya-cu.ac.jp
authors.forename: M
authors.initials: M
authors.lastname: Tohkin
authors.forename: N
authors.initials: N
authors.lastname: Kaniwa
authors.forename: Y
authors.initials: Y
authors.lastname: Saito
authors.forename: E
authors.initials: E
authors.lastname: Sugiyama
authors.forename: K
authors.initials: K
authors.lastname: Kurose
authors.forename: J
authors.initials: J
authors.lastname: Nishikawa
authors.forename: R
authors.initials: R
authors.lastname: Hasegawa
authors.forename: M
authors.initials: M
authors.lastname: Aihara
authors.forename: K
authors.initials: K
authors.lastname: Matsunaga
authors.forename: M
authors.initials: M
authors.lastname: Abe
authors.forename: H
authors.initials: H
authors.lastname: Furuya
authors.forename: Y
authors.initials: Y
authors.lastname: Takahashi
authors.forename: H
authors.initials: H
authors.lastname: Ikeda
authors.forename: M
authors.initials: M
authors.lastname: Muramatsu
authors.forename: M
authors.initials: M
authors.lastname: Ueta
authors.forename: C
authors.initials: C
authors.lastname: Sotozono
authors.forename: S
authors.initials: S
authors.lastname: Kinoshita
authors.forename: Z
authors.initials: Z
authors.lastname: Ikezawa
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000493:Allopurinol / Q000009:adverse effects* / Q000627:therapeutic use; D044466:Asian People / Q000235:genetics; D015415:Biomarkers / Q000378:metabolism; D002896:Chromosomes, Human, Pair 6 / Q000187:drug effects / Q000235:genetics; D064420:Drug-Related Side Effects and Adverse Reactions; D005260:Female; D055106:Genome-Wide Association Study / Q000379:methods; D006680:HLA Antigens / Q000235:genetics / Q000378:metabolism; D006801:Humans; D015810:Linkage Disequilibrium; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D012867:Skin / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D013262:Stevens-Johnson Syndrome / Q000139:chemically induced / Q000209:etiology / Q000235:genetics* / Q000378:metabolism
chemical_list: D015415:Biomarkers; D006680:HLA Antigens; D000493:Allopurinol