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

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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

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zonisamide
Stevens-Johnson Syndrome
Anticonvulsants
Phenobarbital
HLA-A Antigens
Phenytoin
Biomarkers
HLA-DRB1 Chains
HLA-B Antigens
Healthy Volunteers

All Science Journal Classification (ASJC) codes

  • Molecular Medicine
  • Genetics
  • Pharmacology

Cite this

Kaniwa, Nahoko ; Sugiyama, Emiko ; Saito, Yoshiro ; Kurose, Kouichi ; Maekawa, Keiko ; Hasegawa, Ryuichi ; Furuya, Hirokazu ; Ikeda, Hiroko ; Takahashi, Yukitoshi ; Muramatsu, Masaaki ; Tohkin, Masahiro ; Ozeki, Takeshi ; Mushiroda, Taisei ; Kubo, Michiaki ; Kamatani, Naoyuki ; Abe, Masamichi ; Yagami, Akiko ; Ueta, Mayumi ; Sotozono, Chie ; Kinoshita, Shigeru ; Ikezawa, Zenro ; Matsunaga, Kayoko ; Aihara, Michiko. / Specific HLA types are associated with antiepileptic drug-induced Stevens-Johnson syndrome and toxic epidermal necrolysis in Japanese subjects. In: Pharmacogenomics. 2013 ; Vol. 14, No. 15. pp. 1821-1831.
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title = "Specific HLA types are associated with antiepileptic drug-induced Stevens-Johnson syndrome and toxic epidermal necrolysis in Japanese subjects",
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.",
author = "Nahoko Kaniwa and Emiko Sugiyama and Yoshiro Saito and Kouichi Kurose and Keiko Maekawa and Ryuichi Hasegawa and Hirokazu Furuya and Hiroko Ikeda and Yukitoshi Takahashi and Masaaki Muramatsu and Masahiro Tohkin and Takeshi Ozeki and Taisei Mushiroda and Michiaki Kubo and Naoyuki Kamatani and Masamichi Abe and Akiko Yagami and Mayumi Ueta and Chie Sotozono and Shigeru Kinoshita and Zenro Ikezawa and Kayoko Matsunaga and Michiko Aihara",
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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, Kinoshita, S, Ikezawa, Z, Matsunaga, K & Aihara, M 2013, 'Specific HLA types are associated with antiepileptic drug-induced Stevens-Johnson syndrome and toxic epidermal necrolysis in Japanese subjects', Pharmacogenomics, vol. 14, no. 15, pp. 1821-1831. https://doi.org/10.2217/PGS.13.180

Specific HLA types are associated with antiepileptic drug-induced Stevens-Johnson syndrome and toxic epidermal necrolysis in Japanese subjects. / Kaniwa, Nahoko; Sugiyama, Emiko; Saito, Yoshiro; Kurose, Kouichi; Maekawa, Keiko; Hasegawa, Ryuichi; Furuya, Hirokazu; Ikeda, Hiroko; Takahashi, Yukitoshi; Muramatsu, Masaaki; Tohkin, Masahiro; Ozeki, Takeshi; Mushiroda, Taisei; Kubo, Michiaki; Kamatani, Naoyuki; Abe, Masamichi; Yagami, Akiko; Ueta, Mayumi; Sotozono, Chie; Kinoshita, Shigeru; Ikezawa, Zenro; Matsunaga, Kayoko; Aihara, Michiko.

In: Pharmacogenomics, Vol. 14, No. 15, 01.11.2013, p. 1821-1831.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Specific HLA types are associated with antiepileptic drug-induced Stevens-Johnson syndrome and toxic epidermal necrolysis in Japanese subjects

AU - Kaniwa, Nahoko

AU - Sugiyama, Emiko

AU - Saito, Yoshiro

AU - Kurose, Kouichi

AU - Maekawa, Keiko

AU - Hasegawa, Ryuichi

AU - Furuya, Hirokazu

AU - Ikeda, Hiroko

AU - Takahashi, Yukitoshi

AU - Muramatsu, Masaaki

AU - Tohkin, Masahiro

AU - Ozeki, Takeshi

AU - Mushiroda, Taisei

AU - Kubo, Michiaki

AU - Kamatani, Naoyuki

AU - Abe, Masamichi

AU - Yagami, Akiko

AU - Ueta, Mayumi

AU - Sotozono, Chie

AU - Kinoshita, Shigeru

AU - Ikezawa, Zenro

AU - Matsunaga, Kayoko

AU - Aihara, Michiko

PY - 2013/11/1

Y1 - 2013/11/1

N2 - 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.

AB - 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.

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U2 - 10.2217/PGS.13.180

DO - 10.2217/PGS.13.180

M3 - Article

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AN - SCOPUS:84893344987

VL - 14

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JF - Pharmacogenomics

SN - 1462-2416

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