Specific HLA types are associated with antiepileptic drug-induced Stevens-Johnson syndrome and toxic epidermal necrolysis in Japanese subjects

Nahoko Kaniwa, Emiko Sugiyama, Yoshiro Saito, Kouichi Kurose, Keiko Maekawa, Ryuichi Hasegawa, Hirokazu Furuya, Hiroko Ikeda, Yukitoshi Takahashi, Masaaki Muramatsu, Masahiro Tohkin, Takeshi Ozeki, Taisei Mushiroda, Michiaki Kubo, Naoyuki Kamatani, Masamichi Abe, Akiko Yagami, Mayumi Ueta, Chie Sotozono, Shigeru KinoshitaZenro Ikezawa, Kayoko Matsunaga, Michiko Aihara

Research output: Contribution to journalArticle

29 Citations (Scopus)

Abstract

This preliminary study investigated genomic biomarkers for Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN), related to three antiepileptic drugs, zonisamide, phenobarbital and phenytoin. Patients & methods: HLA class I and HLA-DRB1 loci were genotyped for Japanese patients with zonisamide-, phenobarbital- or phenytoin-induced SJS/TEN (n = 12, 8 and 9, respectively) and for healthy Japanese volunteers (n = 2878). Results: Carrier frequencies of HLA-A*02:07 in patients with zonisamide-induced SJS/TEN and in the general Japanese population were 41.7 and 6.81%, respectively. Carrier frequencies of HLA-B*51:01 in patients with phenobarbital- and phenytoin-induced SJS/TEN and in controls were 75.0, 55.6 and 15.2%, respectively. HLA-A*02:07 and HLA-B*51:01, in a dominant model, were significantly associated with zonisamide- and phenobarbital-induced SJS/TEN, respectively (Pc = 0.0176 and 0.0042, respectively). Conclusion: Our data suggest that HLA-A*02:07 and HLA-B*51:01 are potential biomarkers for zonisamide- and phenobarbital-induced SJS/TEN, respectively, in Japanese individuals.

Original languageEnglish
Pages (from-to)1821-1831
Number of pages11
JournalPharmacogenomics
Volume14
Issue number15
DOIs
Publication statusPublished - 01-11-2013

    Fingerprint

All Science Journal Classification (ASJC) codes

  • Molecular Medicine
  • Genetics
  • Pharmacology

Cite this

Kaniwa, N., Sugiyama, E., Saito, Y., Kurose, K., Maekawa, K., Hasegawa, R., Furuya, H., Ikeda, H., Takahashi, Y., Muramatsu, M., Tohkin, M., Ozeki, T., Mushiroda, T., Kubo, M., Kamatani, N., Abe, M., Yagami, A., Ueta, M., Sotozono, C., ... Aihara, M. (2013). Specific HLA types are associated with antiepileptic drug-induced Stevens-Johnson syndrome and toxic epidermal necrolysis in Japanese subjects. Pharmacogenomics, 14(15), 1821-1831. https://doi.org/10.2217/PGS.13.180