Allopurinol, an inhibitor of xanthine oxidase, is widely used for the treatment of hyperuricemia associated with chronic gout, acute uric acid nephropathy, recurrent uric acid stone formation, certain enzyme/blood disorders, and cancer chemotherapy. It has been shown that severe cutaneous adverse drug reactions (ADRs) caused by allopurinol were strongly associated with HLA-B*58:01 in a Han Chinese sample population [
]. Odds ratio (OR) for the association of HLA-B*58:01 with allopurinol-induced severe cutaneous ADR in this population was 580.3 and 95% CI was 34.4–9780.9. Although the relationship between HLA-B*58:01 and allopurinol-induced Stevens–Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) has subsequently been studied in European and Japanese patients, the association was much weaker than that reported in Han Chinese patients [
- Hung S.I.
- Chung W.H.
- Liou L.B.
- Chu C.C.
- Lin M.
- Huang H.P.
- et al.
HLA-B*5801 allele as a genetic marker for severe cutaneous adverse reactions caused by allopurinol.
Proc Natl Acad Sci U S A. 2005; 102: 4134-4139
- Lonjou C.
- Borot N.
- Sekula P.
- Ledger N.
- Thomas L.
- Halevy S.
- et al.
A European study of HLA-B in Stevens–Johnson syndrome and toxic epidermal necrolysis related to five high-risk drugs.
Pharmacogenet Genomics. 2008; 18: 99-107
3]. The association study in Japanese patients was examined in only a limited number of allopurinol-induced ADR cases. We therefore conducted a case-controlled study to determine HLA types associated with allopurinol-induced ADR in a Japanese sample population.
- Tohkin M.
- Kaniwa N.
- Saito Y.
- Sugiyama E.
- Kurose K.
- Nishikawa J.
- et al.
A whole-genome association study of major determinants for allopurinol-related Stevens–Johnson syndrome and toxic epidermal necrolysis in Japanese patients.
Pharmacogenomics J. 2013; 13: 60-67
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- HLA-B*5801 allele as a genetic marker for severe cutaneous adverse reactions caused by allopurinol.Proc Natl Acad Sci U S A. 2005; 102: 4134-4139
- A European study of HLA-B in Stevens–Johnson syndrome and toxic epidermal necrolysis related to five high-risk drugs.Pharmacogenet Genomics. 2008; 18: 99-107
- A whole-genome association study of major determinants for allopurinol-related Stevens–Johnson syndrome and toxic epidermal necrolysis in Japanese patients.Pharmacogenomics J. 2013; 13: 60-67
- The spectrum of Stevens–Johnson syndrome and toxic epidermal necrolysis: a clinical classification.J Invest Dermatol. 1994; 102: 28-30
- HLA-A31 strongly associates with carbamazepine-induced adverse drug reactions but not with carbamazepine-induced lymphocyte proliferation in a Japanese population.J Dermatol. 2012; 39: 594-601
- Association of HLA-B*5801 allele and allopurinol-induced Stevens Johnson syndrome and toxic epidermal necrolysis: a systematic review and meta-analysis.BMC Med Genet. 2011; 12: 118
- Medical genetics: a marker for Stevens–Johnson syndrome.Nature. 2004; 428: 486
- Cost-effectiveness of HLA-B*1502 genotyping in adult patients with newly diagnosed epilepsy in Singapore.Neurology. 2012; 18: 1259-1267
Published online: May 13, 2013
Received: November 22, 2012
© 2013 Japanese Society for Investigative Dermatology. Published by Elsevier Inc. All rights reserved.