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Pathway genes and metabolites in thiopurine therapy in Korean children with acute lymphoblastic leukaemia
Author(s) -
Choi Rihwa,
Sohn Insuk,
Kim MinJi,
Woo Hye In,
Lee Ji Won,
Ma Youngeun,
Yi Eun Sang,
Koo Hong Hoe,
Lee SooYoun
Publication year - 2019
Publication title -
british journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.216
H-Index - 146
eISSN - 1365-2125
pISSN - 0306-5251
DOI - 10.1111/bcp.13943
Subject(s) - thiopurine methyltransferase , itpa , medicine , genotyping , mercaptopurine , genotype , slco1b1 , methylenetetrahydrofolate reductase , neutropenia , pharmacogenetics , oncology , genetics , gene , biology , chemotherapy , azathioprine , disease , ribavirin
Aims We aimed to investigate the impact of various genetic polymorphisms affecting thiopurine metabolism pathways and toxicity in paediatric acute lymphoblastic leukaemia patients for the first time in Korea. Methods From May 2006 to September 2016, 139 paediatric acute lymphoblastic leukaemia patients treated with combination chemotherapy including 6‐mercaptopurine were included in the study. One hundred and twenty‐three variants in 43 genes, including TMPT and NUDT15 , were screened using targeted genotyping, such as a MassARRAY system, direct sequencing and polymerase chain reaction‐restriction fragment length polymorphism methods. Among the polymorphisms screened, 103 polymorphisms of 43 genes were included for further analyses. Results The genetic polymorphisms in the ABCC4 , AHCY , ATIC , FAM8A6P , GART , GNG2 , GSTA1 , MTHFD1 , MTHFR , NUDT15 , PACSIN2 , TYMS and XDH genes, and an intronic polymorphism between HIVEP2 and AIG1 , and TPMT genotype were associated with thiopurine metabolism ( P < 0.05). Genetic polymorphisms in the ABCC4 , ADK , ATIC , GART , GMPS , GSTP1 , IMPDH1 , ITPA , KCNMA1 , MOCOS , MTRR , NUDT15 , SLC19A1 , SLC28A3 , SLC29A1 , SLCO1B1 , TYMP and XDH genes were associated with thiopurine‐related toxicities; neutropenia, hepatotoxicity and treatment interruption ( P < 0.05). Conclusions Findings of this study may provide basic knowledge for personalized medicine for thiopurinxe treatment in paediatric acute lymphoblastic leukaemia patients.