Strong association between HLA-B*5801 and allopurinol-induced Stevens-Johnson syndrome and toxic epidermal necrolysis in a Thai population

Objectives Allopurinol, a uric acid lowering drug commonly used for hyperuricemia and gouty arthritis, has been reported as a common cause of severe cutaneous adverse drug reactions (SCAR) including Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN). A strong association between allopurinol-induced SCAR and HLA-B*5801 was observed in a Han Chinese population with high frequency of this allele, whereas only a moderate association was observed in populations with low frequency (i.e. European and Japanese). This study investigated the relationship between SJS/TEN and HLA-B*5801 in a Thai population that has a high allelic frequency of this allele. Methods Twenty-seven allopurinol-induced SJS/TEN and 54 allopurinol-tolerant patients were enrolled in the study. The presence of HLA-B*5801 and HLA-B genotypes in these patients were analyzed using a PG5801 DNA detection kit and sequence-based typing, respectively. Results All of the 27 (100%) allopurinol-induced SJS/TEN patients who were examined carried HLA-B*5801 only seven (12.96%) of the control patients had this The risk of allopurinol-induced SJS/TEN was significantly greater in patients with HLA-B*5801 when compared wit those who did not carry this allele, with an odds ratio of 348.3 (95% confidence interval=19.2-6336.9, P=1.6 x 10(-13)). The sensitivity and specificity of the HLA-B*5801 allele for prediction of allopurinol-induced SJS/TEN were 100 and 87%, respectively. By assuming a 0.2% prevalence rate, the positive predictive value and the negative predictive value of the HLA-B*5801 allele was 1.52 and 100%, respectively. Conclusion A strong association of allopurinol-induced SJS/TEN with the HLA-B*5801 allele was observed in a Thai population. The results suggest that HLA-B*5801 is a valid genetic marker for screening Thai individuals who may be at risk for allopurinol-induced life-threatening SJS and TEN. Pharmacogenetics and Genomics 19:704-709 (C) 2009 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins.