title: Association of troglitazone-induced liver injury with mutation of the cytochrome P450 2C19 gene.
abstract: An anti-diabetic agent, troglitazone, was withdrawn from the market because of its association with liver injury. However, the mechanism of the injury has not been elucidated. We examined, retrospectively, the frequency of the polymorphisms of the cytochrome P450 (CYP) 2C19 and 2D6 genes in eight patients with type 2 diabetes who had troglitazone-induced liver injury and 31 subjects who tolerated troglitazone well. Polymorphisms of CYP 2C19 and 2D6 genes were analyzed by polymerase chain reaction using peripheral white blood cells. The incidence of mutations was compared with known population data for the Japanese. Homozygous or compound heterozygous mutations in CYP 2C19 alleles were found in four of the eight (50.0%) patients with troglitazone-induced liver injury. This rate was significantly higher than that in patients without liver injury (four of 31, 12.9%). The frequency of P450 2D6 mutations was the same in both groups. In conclusion, troglitazone-induced liver injury occurred more frequently in subjects with the CYP 2C19 mutations in Japanese patients.
authors.affiliation: The Second Department of Medicine, Kurume University, School of Medicine, 67 Asahimachi, Fukuoka 830-0011, Kurume, Japan
authors.forename: Ryukichi
authors.initials: R
authors.lastname: Kumashiro
authors.forename: Takahiro
authors.initials: T
authors.lastname: Kubota
authors.forename: Yuriko
authors.initials: Y
authors.lastname: Koga
authors.forename: Masatoshi
authors.initials: M
authors.lastname: Tanaka
authors.forename: Chizuko
authors.initials: C
authors.lastname: Inada
authors.forename: Nobuhide
authors.initials: N
authors.lastname: Kusaba
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Yoshida
authors.forename: Akiko
authors.initials: A
authors.lastname: Hisamochi
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Ide
authors.forename: Yuko
authors.initials: Y
authors.lastname: Tomita
authors.forename: Naoko
authors.initials: N
authors.lastname: Masumoto
authors.forename: Kyuichi
authors.initials: K
authors.lastname: Tanikawa
authors.forename: Tatsuji
authors.initials: T
authors.lastname: Iga
authors.forename: Michio
authors.initials: M
authors.lastname: Sata