Enhanced susceptibility of HLA-mediated ticlopidine-induced idiosyncratic hepatotoxicity by CYP2B6 polymorphism in Japanese

Noritaka Ariyoshi, Yukako Iga, Koji Hirata, Yasunori Sato, Go Miura, Itsuko Ishii, Seiji Nagamori, Mitsukazu Kitada

研究成果: Article査読

35 被引用数 (Scopus)

抄録

Hepatotoxicity is the most frequent adverse drug reaction (ADR) in Japanese treated with ticlopidine (TP). We investigated the relationship between CYP2B6 haplotype and incidence of TP-induced hepatotoxicity in 114 Japanese patients. Although 4 haplotypes (*1A, *1H, *1J and *6B) accounted for more than 80z of the inferred haplotypes in both control (n=81) and case (n=22) subjects, the prevalence was apparently different: control, *1AA>*6BA>*1HA>*1J and case, *1JA>*1HA>*1AA>*6B. The reporter gene assay for the two SNPs, which comprise the *1H or *1J haplotype, suggested that the *1H and *1J haplotypes may be associated with the increased expression of CYP2B6, probably due to g.-2320TÀC. Combination analysis of CYP2B6 and human leukocyte antigen (HLA) haplotypes revealed that individuals possessing CYP2B6*1H or *1J with HLA-A*3303 have the highest susceptibility to TP-induced hepatotoxicity (odds ratio, 38.82;95zCI, 8.08-196.0, Po0.001). Although this is a preliminary case-control study with some limitations, it is the first example that HLA-induced idiosyncratic ADR may be modified by individual variation in CYP activities.

本文言語English
ページ(範囲)298-306
ページ数9
ジャーナルDrug Metabolism And Pharmacokinetics
25
3
DOI
出版ステータスPublished - 2010
外部発表はい

ASJC Scopus subject areas

  • 薬理学
  • 薬科学
  • 薬理学(医学)

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