Positive and negative associations of HLA class I alleles with allopurinol-induced SCARs in Koreans

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.This study was supported by a Grant from the Korea Health 21 R&D Project, Ministry of Health & Welfare, Korea (Grant No. 03-PJ10-PG13-GD01-0002)