Allopurinol, a commonly prescribed medication for gout and hyperuricemia, is a 
frequent cause of severe cutaneous adverse reactions (SCAR), which include the 
drug hypersensitivity syndrome, Stevens-Johnson syndrome, and toxic epidermal 
necrolysis. The adverse events are unpredictable and carry significant morbidity 
and mortality. To identify genetic markers for allopurinol-SCAR, we carried out 
a case-control association study. We enrolled 51 patients with allopurinol-SCAR 
and 228 control individuals (135 allopurinol-tolerant subjects and 93 healthy 
subjects from the general population), and genotyped for 823 SNPs in genes 
related to drug metabolism and immune response. The initial screen revealed 
strong association between allopurinol-SCAR and SNPs in the MHC region, 
including BAT3 (encoding HLA-B associated transcript 3), MSH5 (mutS homolog 5), 
and MICB (MHC class I polypeptide-related sequence B) (P < 10(-7)). We then 
determined the alleles of HLA loci A, B, C, and DRB1. The HLA-B*5801 allele was 
present in all (100%) 51 patients with allopurinol-SCAR, but only in 20 (15%) of 
135 tolerant patients [odds ratio 580.3 (95% confidence interval, 34.4-9780.9); 
corrected P value = 4.7 x 10(-24)] and in 19 (20%) of 93 of healthy subjects 
[393.51 (23.23-6665.26); corrected P value = 8.1 x 10(-18)]. HLA alleles A*3303, 
Cw*0302, and DRB1*0301 were in linkage disequilibrium and formed an extended 
haplotype with HLA-B*5801. Our results indicated that allopurinol-SCAR is 
strongly associated with a genetic predisposition in Han Chinese. In particular, 
HLA-B*5801 allele is an important genetic risk factor for this life-threatening 
condition.