Methylenetetrahydrofolate reductase C677T and A1298C gene polymorphisms and therapy-related toxicity in children treated for acute lymphoblastic leukemia and non-Hodgkin lymphoma.

Kantar M., Kosova B., Cetingul N., Gumus S., Toroslu E., Zafer N., ...Daha Fazla

Leukemia & lymphoma, cilt.50, ss.912-7, 2009 (SCI-Expanded) identifier identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 50
  • Basım Tarihi: 2009
  • Doi Numarası: 10.1080/10428190902893819
  • Dergi Adı: Leukemia & lymphoma
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus
  • Sayfa Sayıları: ss.912-7
  • Anahtar Kelimeler: Methotrexate, MTHFR, polymorphism, toxicity, children, MTHFR POLYMORPHISMS, COMMON MUTATION, METHOTREXATE, RISK, SUSCEPTIBILITY, ASSOCIATION, ALLELE, NHL
  • Akdeniz Üniversitesi Adresli: Hayır

Özet

This study aimed to investigate the association of the methylenetetrahydrofolate reductase (MTHFR) gene C677T and A1298C polymorphisms with serum drug levels and toxicities after high-dose methotrexate (MTX) infusion. The study included 37 children with acute lymphoblastic leukemia or non-Hodgkin lymphoma. Serum MTX levels and toxicities of bone marrow, liver and kidney were analysed. Genotype analysis of the C677T and A1298C gene polymorphisms from genomic DNA of the subjects was performed by real-time PCR. Subjects with MTHFR polymorphism for C677T (CT, TT) had significantly higher MTX levels at 24h (p=0.009), and these genotypes did not seem to cause toxicity. Subjects with MTHFR polymorphism for A1298C (AC, CC) had significantly higher MTX levels at 48h (p=0.02), and had more grade III/IV anemia (p=0.02), thrombocytopenia (p=0.0001), elevated AST levels (p=0.04) and frequent febrile neutropenic episodes (p=0.004). The present study suggests that A1298C gene, but not C677T polymorphism is associated with MTX-related toxicity.