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

• Published in: Pharmacogenomics Vol. 14; no. 15; pp. 1821 - 1831
• Main Authors: 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
• Format: Journal Article
• Language: English
• Published: England Future Medicine Ltd 01.11.2013
• Subjects: Adolescent; Adult; Aged; Anticonvulsants - adverse effects; aromatic antiepileptic drug; Asian Continental Ancestry Group - genetics; Biomarkers; Child; Child, Preschool; Drug-Related Side Effects and Adverse Reactions - genetics; Drugs; Female; Genotype; Histocompatibility antigens; HLA histocompatibility antigens; HLA-DRB1 Chains - genetics; Humans; Male; Middle Aged; Phenobarbital; Phenytoin; Stevens-Johnson syndrome; Stevens-Johnson Syndrome - genetics; toxic epidermal necrolysis; zonisamide; Japan; Taiwan
• ISSN: 1462-2416; 1744-8042; 1744-8042
• DOI: 10.2217/pgs.13.180

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. class I and 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). Carrier frequencies of in patients with zonisamide-induced SJS/TEN and in the general Japanese population were 41.7 and 6.81%, respectively. Carrier frequencies of in patients with phenobarbital- and phenytoin-induced SJS/TEN and in controls were 75.0, 55.6 and 15.2%, respectively. and , in a dominant model, were significantly associated with zonisamide- and phenobarbital-induced SJS/TEN, respectively (Pc = 0.0176 and 0.0042, respectively). Our data suggest that and are potential biomarkers for zonisamide- and phenobarbital-induced SJS/TEN, respectively, in Japanese individuals. Original submitted 25 April 2013; Revision submitted 11 September 2013