Study on the relationship between genetic polymorphism of TPMT and ITPA with adverse drug reactions in 6-mercaptopurine treatment

OBJECTIVE To study the relationship between genetic polymorphism of thiopurine methyltransferase(TPMT) and inosine triphosphate pyrophosphatase (ITPA) with adverse drug reactions in 6-mercaptopurine in maintenance treatment of childhood acute lymphoblastic leukemia.METHODS Method of the allele specific PCR(ASPCR) and PCR-restriction fragment length polymorphism(PCR-RFLP) analysis the polymorphism of thiopurine methyltransferase(TPMT) and inosine triphosphate pyrophosphatase(ITPA),HPLC was used for the determination of TPMT and ITPA activity,reference to the adverse reactions of SFDA standards was taken as the ref erence for evaluation of the adverse reactions of 6-mercaptopurine treatment in children with acute lymphoblastic leukemia.RESULTS Risk of bone marrow suppression of TPMT * 3C is higher than wild genome.It was not found that the gene TPMT and ITPA polymorphisms linked with liver damage and gastrointestinal reactions.CONCLUSION Dosage adjustment in TPMT gene mutation can avoid the occurrence of bone marrow suppression.The relationship between TPMT and ITPA polymorphism and 6-mercaptopurine still need to integrate drug interactions with other drug metabolism enzymes in further study of genetic polymorphism.