الفهرس 
Investigating the combined effect of hepatitis C viral infection and the genetic polymorphisms on the Adverse events of methotrexate and 6-mercaptopurine in childhood acute lymphoblastic leukemia
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Abstract
Background: The aim of the present study is to determine the correlation of HCV infection and polymorphisms in different genes with toxicity of either MTX or 6-MP administered to children with ALL. Methods: A hundred children with low risk ALL who were treated according to the St. Jude Total therapy XV were recruited. The recruited children were receiving MTX and 6-MP during maintenance phase. Patients were excluded from the study if they had other types of leukemia. Genotyping analyses for the TPMT, MTHFR, and GST genes were performed using a combination of PCR and PCR-RFLP protocols. Relevant clinical data on adverse drug reactions were collected objectively (blinded to genotypes) from the patient medical records. Results: There was a significant correlation between the combined presence of HCV and TPMT*3B G460A gene polymorphisms and grade 2-4 AST hepatotoxicity (p < 0.04). The same observation was seen when comparing either the presence of HCV alone or the presence of the gene polymorphism alone. A significant association between the combined presence of HCV and MTHFR C677T polymorphism and grades 2-4 ALT, AST, and ALP hepatotoxicity was observed (p values < 0.001, 0.02 and 0.001 respectively). The presence of HCV infection had a significant negative effect on hepatic transaminases