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


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).


CONCLUSIONS
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.
Division of Medicinal Safety Science, National Institute of Health Sciences, 1-18-1 Kamiyoga, Setagaya-ku, Tokyo 158-8501, Japan and The Japan Severe Adverse Reactions (JSAR) Research Group, Tokyo, Japan. nkaniwa@nihs.go.jp.
Nahoko
N
Kaniwa
Emiko
E
Sugiyama
Yoshiro
Y
Saito
Kouichi
K
Kurose
Keiko
K
Maekawa
Ryuichi
R
Hasegawa
Hirokazu
H
Furuya
Hiroko
H
Ikeda
Yukitoshi
Y
Takahashi
Masaaki
M
Muramatsu
Masahiro
M
Tohkin
Takeshi
T
Ozeki
Taisei
T
Mushiroda
Michiaki
M
Kubo
Naoyuki
N
Kamatani
Masamichi
M
Abe
Akiko
A
Yagami
Mayumi
M
Ueta
Chie
C
Sotozono
Shigeru
S
Kinoshita
Zenro
Z
Ikezawa
Kayoko
K
Matsunaga
Michiko
M
Aihara
D000293:Adolescent; D000328:Adult; D000368:Aged; D000927:Anticonvulsants / Q000009:adverse effects*; D044466:Asian People / Q000235:genetics*; D015415:Biomarkers; D002648:Child; D002675:Child, Preschool; D064420:Drug-Related Side Effects and Adverse Reactions / Q000235:genetics*; D005260:Female; D005838:Genotype; D059811:HLA-DRB1 Chains / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D013262:Stevens-Johnson Syndrome / Q000235:genetics*
D000927:Anticonvulsants; D015415:Biomarkers; D059811:HLA-DRB1 Chains