title: Meta-analysis of the impact of thioprineS-methyltransferase polymorphisms on the tolerable 6-mercaptopurine dose considering initial dose and ethnic difference.
abstract: A meta-analysis was conducted to decide whether to reduce an initial 6-mercaptopurine (6-MP) dose inTPMTheterozygote in the case of an initial 6-MP dose of <75 mg/m2/d and to compare the tolerable 6-MP dose among different ethnic groups. The study was undertaken according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. The differences in mean values of the tolerable 6-MP dose were calculated by using Comprehensive Meta-Analysis version 3. The results of the meta-analysis indicated that the tolerable 6-MP dose was significantly lower in theTPMTheterozygote group (difference in mean values =11.729, 95% confidence interval =7.617-15.842,P<0.001) even when the initial 6-MP dose was <75 mg/m2/d. TheTPMT*3Callele-dominant ethnic group (Asian) needed less reduction in mean 6-MP dose in comparison to theTPMT*3Aallele-dominant ethnic group (Caucasian, Mediterranean, South American) (difference in mean values =8.884 vs 15.324). In conclusion, the initial 6-MP dose needs to be reduced inTPMTheterozygote when compared to the wild-type, and ethnic difference might influence the tolerable 6-MP dose inTPMTheterozygotes.
authors.affiliation: College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University, Seoul, Korea.
authors.forename: Myeong Gyu
authors.initials: MG
authors.lastname: Kim
authors.affiliation: College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University, Seoul, Korea.
authors.forename: Minoh
authors.initials: M
authors.lastname: Ko
authors.affiliation: College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University, Seoul, Korea.
authors.forename: In-Wha
authors.initials: IW
authors.lastname: Kim
authors.affiliation: College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University, Seoul, Korea.
authors.forename: Jung Mi
authors.initials: JM
authors.lastname: Oh
keywords: 6-mercaptopurine; meta-analysis; polymorphism; thiopurine S-methyltransferase