Association of troglitazone-induced liver injury with mutation of the cytochrome P450 2C19 gene.
An anti-diabetic agent, troglitazone, was withdrawn from the market because of its association with liver injury.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.
Kumashiro
Ryukichi
R
The Second Department of Medicine, Kurume University, School of Medicine, 67 Asahimachi, Fukuoka 830-0011, Kurume, Japan
Kubota
Takahiro
T
Koga
Yuriko
Y
Tanaka
Masatoshi
M
Inada
Chizuko
C
Kusaba
Nobuhide
N
Yoshida
Hiroshi
H
Hisamochi
Akiko
A
Ide
Tatsuya
T
Tomita
Yuko
Y
Masumoto
Naoko
N
Tanikawa
Kyuichi
K
Iga
Tatsuji
T
Sata
Michio
M