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• W2098481310 abstract "Aim: The rationale of this study was to explore the contribution of genetic variants of the folate pathway to toxicity of 6-mercaptopurine (6-MP)-mediated hematological toxicity in children with acute lymphoblastic leukemia (ALL) and to explore the interaction of these variants with TPMT and ITPA haplotypes using multifactor dimensionality reduction analysis. Materials & methods: Children with ALL (n = 96) were screened for GCPII C1561T, RFC1 G80A, cSHMT C1420T, TYMS 5´-UTR 2R3R, TYMS 3´-UTR ins6/del6, MTHFR C677T, MTR A2756G polymorphisms using PCR-RFLP and PCR-amplified fragment length polymorphism techniques. Results: GCPII C1561T showed independent association with toxicity. The following synergetic interactions appeared to increase the toxicity of 6-mercaptopurine: TPMT*12 × RFC1 G80A; TPMT CTTAT haplotype × RFC1 G80A; TPMT CTTAT haplotype × RFC1 G80A × TYMS 2R3R. The genetic variants of thiopurine and folate pathway cumulatively appeared to increase the predictability of toxicity (r 2 = 0.41) in a multiple linear regression model. For the observed toxicity grades of 1, 2, 3 and 4, the respective predicted toxicity grades were 1.65 ± 0.29, 1.68 ± 0.24, 2.56 ± 0.58 and 2.99 ± 1.03, p trend < 0.0001. Conclusion: Gene–gene interaction between thiopurine and folate pathways inflate the 6-MP-mediated toxicity in Indian children with ALL illustrating the importance of ethnicity in the toxicity of 6-MP. Original submitted 3 January 2012; Revision submitted 23 April 2012" @default.
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• W2098481310 date "2012-07-01" @default.
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• W2098481310 title "Genetic variants of thiopurine and folate metabolic pathways determine 6-MP-mediated hematological toxicity in childhood ALL" @default.
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• W2098481310 doi "https://doi.org/10.2217/pgs.12.70" @default.
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