A whole-genome association study of major determinants for allopurinol-related Stevens-Johnson syndrome and toxic epidermal necrolysis in Japanese patients

M. Tohkin, N. Kaniwa, Y. Saito, E. Sugiyama, K. Kurose, J. Nishikawa, R. Hasegawa, M. Aihara, K. Matsunaga, M. Abe, H. Furuya, Y. Takahashi, H. Ikeda, M. Muramatsu, M. Ueta, C. Sotozono, S. Kinoshita, Z. Ikezawa

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Abstract

Stevens-Johnson syndrome and toxic epidermal necrolysis (SJS/TEN) are severe, cutaneous adverse drug reactions that are rare but life threatening. Genetic biomarkers for allopurinol-related SJS/TEN in Japanese were examined in a genome-wide association study in which Japanese patients (n=14) were compared with ethnically matched healthy controls (n=991). Associations between 890 321 single nucleotide polymorphisms and allopurinol-related SJS/TEN were analyzed by the Fisher's exact test (dominant genotype mode). A total of 21 polymorphisms on chromosome 6 were significantly associated with allopurinol-related SJS/TEN. The strongest association was found at rs2734583 in BAT1, rs3094011 in HCP5 and GA005234 in MICC (P=2.44 × 10-8; odds ratio=66.8; 95% confidence interval, 19.8-225.0). rs9263726 in PSORS1C1, also significantly associated with allopurinol-related SJS/TEN, is in absolute linkage disequilibrium with human leukocyte antigen-B*5801, which is in strong association with allopurinol-induced SJS/TEN. The ease of typing rs9263726 makes it a useful biomarker for allopurinol-related SJS/TEN in Japanese.

Original languageEnglish
Pages (from-to)60-69
Number of pages10
JournalPharmacogenomics Journal
Volume13
Issue number1
DOIs
Publication statusPublished - 02-2013

All Science Journal Classification (ASJC) codes

  • Molecular Medicine
  • Genetics
  • Pharmacology

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    Tohkin, M., Kaniwa, N., Saito, Y., Sugiyama, E., Kurose, K., Nishikawa, J., Hasegawa, R., Aihara, M., Matsunaga, K., Abe, M., Furuya, H., Takahashi, Y., Ikeda, H., Muramatsu, M., Ueta, M., Sotozono, C., Kinoshita, S., & Ikezawa, Z. (2013). A whole-genome association study of major determinants for allopurinol-related Stevens-Johnson syndrome and toxic epidermal necrolysis in Japanese patients. Pharmacogenomics Journal, 13(1), 60-69. https://doi.org/10.1038/tpj.2011.41