title: Association Between Combined Presence of Hepatitis C Virus and Polymorphisms in Different Genes With Toxicities of Methotrexate and 6-Mercaptopurine in Children With Acute Lymphoblastic Leukemia.
abstract: The aim of the present study is to determine the correlation of hepatitis C virus (HCV) infection and polymorphisms in different genes with toxicity of either methotrexate (MTX) or 6-mercaptopurine (6-MP) administered to children with acute lymphoblastic leukemia (ALL).
  
  
  
  One 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 thiopurine methyltransferase (TPMT), methylenetetrahydrofolate reductase (MTHFR), and glutathione S-transferase (GST) genes were performed using a combination of polymerase chain reaction (PCR) and PCR-RFLP (where RFLP is restriction fragment length polymorphism) protocols. Relevant clinical data on adverse drug reactions were collected objectively (blinded to genotypes) from the patient medical records.
  
  
  
  There was a significant correlation between the combined presence of HCV and TPMT*3B G460A gene polymorphisms and grades 2-4 hepatotoxicity as aspartate aminotransferase (AST) elevation (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 hepatotoxicity as alanine aminotransferase (ALT), AST, and alkaline phosphatase (ALP) elevation 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.
  
  
  
  The present data support a role for combining analysis of genetic variation in drug-metabolizing enzymes and the presence of HCV in the assessment of specific drugs toxicities in multiagent chemotherapeutic treatment regimens.
authors.affiliation: Department of Clinical Pharmacy, National Hepatology and Tropical Medicine Research Institute, Cairo, Egypt.
authors.forename: Doaa H
authors.initials: DH
authors.lastname: Abdelaziz
authors.affiliation: Department of Microbiology and Immunology, Faculty of Pharmacy, Cairo University, Cairo, Egypt.
authors.forename: Noha M
authors.initials: NM
authors.lastname: Elhosseiny
authors.affiliation: Department of Pediatric Oncology, National Cancer Institute, Cairo University, Cairo, Egypt.
authors.forename: Sahar A
authors.initials: SA
authors.lastname: Khaleel
authors.affiliation: Department of Clinical Pharmacy, Faculty of Pharmacy, Cairo University, Cairo, Egypt.
authors.forename: Nirmeen A
authors.initials: NA
authors.lastname: Sabry
authors.affiliation: Department of Microbiology and Immunology, Faculty of Pharmacy, Cairo University, Cairo, Egypt.
authors.forename: Ahmed S
authors.initials: AS
authors.lastname: Attia
authors.affiliation: Department of Pediatrics, Hematology-Oncology Division, Faculty of Medicine, Ain-Shams University, Cairo, Egypt.
authors.forename: Manal H
authors.initials: MH
authors.lastname: El-Sayed
mesh_terms: D002648:Child; D002675:Child, Preschool; D005260:Female; D005838:Genotype; D016174:Hepacivirus / Q000302:isolation & purification*; D006801:Humans; D008099:Liver / Q000187:drug effects; D008297:Male; D015122:Mercaptopurine / Q000009:adverse effects*; D008727:Methotrexate / Q000009:adverse effects*; D042965:Methylenetetrahydrofolate Reductase (NADPH2) / Q000235:genetics; D008780:Methyltransferases / Q000235:genetics; D011110:Polymorphism, Genetic; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy* / Q000235:genetics / Q000821:virology
chemical_list: D015122:Mercaptopurine; D042965:Methylenetetrahydrofolate Reductase (NADPH2); D008780:Methyltransferases; C022745:thiopurine methyltransferase; D008727:Methotrexate
keywords: HCV; acute lymphoblastic leukemia; chemotherapy; children; genetic polymorphism; toxicities