Meta-analysis of the impact of thioprine S-methyltransferase polymorphisms on the tolerable 6-mercaptopurine dose considering initial dose and ethnic difference

A meta-analysis was conducted to decide whether to reduce an initial 6-mercaptopurine (6-MP) dose in TPMT heterozygote 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 the TPMT heterozygote 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. The TPMT*3C allele-dominant ethnic group (Asian) needed less reduction in mean 6-MP dose in comparison to the TPMT*3A allele-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 in TPMT heterozygote when compared to the wild-type, and ethnic difference might influence the tolerable 6-MP dose in TPMT heterozygotes.