title: Positive and negative associations of HLA class I alleles with allopurinol-induced SCARs in Koreans.
abstract: Recent investigations suggest genetic susceptibility of allopurinol-induced severe cutaneous adverse reactions (SCARs). However, the strength of association was variable according to phenotypes and ethnic backgrounds. To explore genetic markers for allopurinol-induced SCARs in Koreans, we genotyped human leukocyte antigen (HLA) class I alleles of 25 cases of allopurinol-induced SCARs (20 cases of drug-induced hypersensitivity syndrome and five cases of Stevens-Johnson syndrome/toxic epidermal necrolysis) and 57 patients tolerant to allopurinol. Frequencies of B*5801 [92.0 vs. 10.5%, P(c)=2.45×10(-11), odds ratio (OR)=97.8], Cw*0302 (92.0 vs. 12.3%, P(c)=9.39×10(-11), OR=82.1), and A*3303 (88.0 vs. 26.3%, P(c)=3.31×10(-6), OR=20.5) were significantly higher in SCARs compared with tolerant controls. In contrast, A*0201 was not found in SCARs patients despite relatively high frequency in tolerant controls (29.8%). We found strong positive association of HLA-B*5801 and negative association of HLA-A*0201 with the development of allopurinol-induced SCARs in the Korean population.
authors.affiliation: Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea.
authors.forename: Hye-Ryun
authors.initials: HR
authors.lastname: Kang
authors.forename: Young Koo
authors.initials: YK
authors.lastname: Jee
authors.forename: Yon-Soo
authors.initials: YS
authors.lastname: Kim
authors.forename: Chang Hwa
authors.initials: CH
authors.lastname: Lee
authors.forename: Jae-Woo
authors.initials: JW
authors.lastname: Jung
authors.forename: Sae Hoon
authors.initials: SH
authors.lastname: Kim
authors.forename: Heung-Woo
authors.initials: HW
authors.lastname: Park
authors.forename: Yoon-Seok
authors.initials: YS
authors.lastname: Chang
authors.forename: In-Jin
authors.initials: IJ
authors.lastname: Jang
authors.forename: Sang-Heon
authors.initials: SH
authors.lastname: Cho
authors.forename: Kyung-Up
authors.initials: KU
authors.lastname: Min
authors.forename: Sang-Heon
authors.initials: SH
authors.lastname: Kim
authors.forename: Kyung Wha
authors.initials: KW
authors.lastname: Lee
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000493:Allopurinol / Q000009:adverse effects* / Q000627:therapeutic use; D044466:Asian People / Q000235:genetics; D005260:Female; D005805:Genes, MHC Class I; D055106:Genome-Wide Association Study; D006074:Gout Suppressants / Q000009:adverse effects* / Q000627:therapeutic use; D006801:Humans; D008297:Male; D008875:Middle Aged; D013262:Stevens-Johnson Syndrome / Q000209:etiology / Q000235:genetics*
chemical_list: D006074:Gout Suppressants; D000493:Allopurinol