PMID- 20610889
OWN - NLM
STAT- MEDLINE
DCOM- 20101012
LR  - 20191111
IS  - 1880-0920 (Electronic)
IS  - 1347-4367 (Linking)
VI  - 25
IP  - 3
DP  - 2010
TI  - Enhanced susceptibility of HLA-mediated ticlopidine-induced idiosyncratic 
      hepatotoxicity by CYP2B6 polymorphism in Japanese.
PG  - 298-306
AB  - 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 80% of the 
      inferred haplotypes in both control (n=81) and case (n=22) subjects, the 
      prevalence was apparently different: control, *1A>*6B>*1H>*1J and case, 
      *1J>*1H>*1A>*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.-2320T>C. 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; 95%CI, 
      8.08-196.0, P<0.001). 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.
FAU - Ariyoshi, Noritaka
AU  - Ariyoshi N
AD  - Division of Pharmacy, University Hospital, Chiba University School of Medicine, 
      1-8-1 Inohana, Chuo-ku, Chiba, Japan. ariyoshi@ho.chiba-u.ac.jp
FAU - Iga, Yukako
AU  - Iga Y
FAU - Hirata, Koji
AU  - Hirata K
FAU - Sato, Yasunori
AU  - Sato Y
FAU - Miura, Go
AU  - Miura G
FAU - Ishii, Itsuko
AU  - Ishii I
FAU - Nagamori, Seiji
AU  - Nagamori S
FAU - Kitada, Mitsukazu
AU  - Kitada M
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Drug Metab Pharmacokinet
JT  - Drug metabolism and pharmacokinetics
JID - 101164773
RN  - 0 (HLA Antigens)
RN  - 0 (Platelet Aggregation Inhibitors)
RN  - EC 1.14.14.1 (Aryl Hydrocarbon Hydroxylases)
RN  - EC 1.14.14.1 (CYP2B6 protein, human)
RN  - EC 1.14.14.1 (Cytochrome P-450 CYP2B6)
RN  - EC 1.5.- (Oxidoreductases, N-Demethylating)
RN  - OM90ZUW7M1 (Ticlopidine)
SB  - IM
MH  - Aryl Hydrocarbon Hydroxylases/*genetics
MH  - Biotransformation/genetics
MH  - Case-Control Studies
MH  - Chemical and Drug Induced Liver Injury/*epidemiology/*genetics
MH  - Cytochrome P-450 CYP2B6
MH  - Enzyme Activation/drug effects
MH  - Genotype
MH  - HLA Antigens/*genetics
MH  - Haplotypes/genetics
MH  - Humans
MH  - Japan/epidemiology/ethnology
MH  - Oxidoreductases, N-Demethylating/*genetics
MH  - Platelet Aggregation Inhibitors/*adverse effects/therapeutic use
MH  - Polymorphism, Single Nucleotide
MH  - Ticlopidine/*adverse effects/therapeutic use
EDAT- 2010/07/09 06:00
MHDA- 2010/10/13 06:00
CRDT- 2010/07/09 06:00
PHST- 2010/07/09 06:00 [entrez]
PHST- 2010/07/09 06:00 [pubmed]
PHST- 2010/10/13 06:00 [medline]
AID - JST.JSTAGE/dmpk/25.298 [pii]
AID - 10.2133/dmpk.25.298 [doi]
PST - ppublish
SO  - Drug Metab Pharmacokinet. 2010;25(3):298-306. doi: 10.2133/dmpk.25.298.