Thawinee JantararoungtongSupaporn WiwattanakulRawiporn TiyasirichokchaiSantirhat PrommasRattanaporn SukprasongNapatrupron KoomdeePimonpan JindaJiratha RachanakulNutthan NuntharadthanaphongSamart PakakasamaUsanarat AnurathapanSuradej HongengChonlaphat SukasemRamathibodi HospitalFaculty of Medicine Ramathibodi Hospital, Mahidol UniversitySrinakharinwirot University2022-08-042022-08-042021-08-01Journal of Personalized Medicine. Vol.11, No.8 (2021)207544262-s2.0-85113156828https://repository.li.mahidol.ac.th/handle/20.500.14594/77989The response to 6-mercaptopurine (6-MP) can be altered by genetic polymorphisms in genes encoding drug-metabolizing enzymes and drug transporters. The purpose of this study was to investigate the association between genetic polymorphisms of drug-metabolizing enzymes (TPMT 719A > G (*3C), ITPA 94C > A and ITPA 123G > A) and drug transporters (MRP4 912C > A and MRP4 2269G > A) with 6-MP-related myelotoxicity and hepatotoxicity in Thai children with acute lymphoblastic leukemia (ALL). The prescribed dosage of 6-MP and its adverse effects were assessed from medical records during the first 8 weeks and 9–24 weeks of maintenance therapy. Children with the TPMT*1/*3C genotype had a higher risk of leukopenia with an odds ratio (OR) of 4.10 (95% confidence interval (CI) of 1.06–15.94; p = 0.033) compared to wild type (TPMT*1/*1) patients. Heterozygous TPMT*3C was significantly associated with severe neutropenia with an increased risk (OR, 4.17; 95% CI, 1.25–13.90); p = 0.014) during the first 8 weeks. No association was found among ITPA 94C > A, ITPA 123G > A, MRP4 912C > A, and MRP4 2269G > A with myelotoxicity and hepatotoxicity. The evidence that TPMT heterozygotes confer risks of 6-MP-induced myelotoxicity also supports the convincing need to genotype this pharmacogenetic marker before the initiation of 6-MP therapy.Mahidol UniversityMedicineArticleSCOPUS10.3390/jpm11080783