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Enhanced Susceptibility of HLA-mediated Ticlopidine-induced Idiosyncratic Hepatotoxicity by CYP2B6Polymorphism in Japanese
- Source :
- Drug Metabolism and Pharmacokinetics; January 2010, Vol. 25 Issue: 3 p298-306, 9p
- Publication Year :
- 2010
-
Abstract
- Hepatotoxicity is the most frequent adverse drug reaction (ADR) in Japanese treated with ticlopidine (TP). We investigated the relationship between CYP2B6haplotype and incidence of TP-induced hepatotoxicity in 114 Japanese patients. Although 4 haplotypes (* 1A,* 1H,* 1Jand *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>* 1Jand case, * 1J>* 1H>* 1A>* 6B.The reporter gene assay for the two SNPs, which comprise the * 1Hor * 1Jhaplotype, suggested that the * 1Hand * 1Jhaplotypes may be associated with the increased expression of CYP2B6, probably due to g. −2320T>C. Combination analysis of CYP2B6and human leukocyte antigen (HLA) haplotypes revealed that individuals possessing CYP2B6* 1Hor * 1Jwith HLA-A*3303have 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.
Details
- Language :
- English
- ISSN :
- 13474367
- Volume :
- 25
- Issue :
- 3
- Database :
- Supplemental Index
- Journal :
- Drug Metabolism and Pharmacokinetics
- Publication Type :
- Periodical
- Accession number :
- ejs36258944
- Full Text :
- https://doi.org/10.2133/dmpk.25.298