Altered expression of methylenetetrahydrofolate reductase modifies response to methotrexate in mice

ÇELTİKÇİ B., Leclerc D., Lawrance A. K., Deng L., Friedman H. C., Krupenko N. I., ...More

PHARMACOGENETICS AND GENOMICS, vol.18, no.7, pp.577-589, 2008 (SCI-Expanded) identifier identifier identifier

  • Publication Type: Article / Article
  • Volume: 18 Issue: 7
  • Publication Date: 2008
  • Doi Number: 10.1097/fpc.0b013e32830058aa
  • Journal Name: PHARMACOGENETICS AND GENOMICS
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus
  • Page Numbers: pp.577-589
  • Hacettepe University Affiliated: Yes

Abstract

Objective Folates provide one-carbon units for nucleotide synthesis and methylation reactions. A common polymorphism (677C -> T) in methylenetetrahydrofolate reductase (MTHFR) encodes an enzyme with reduced activity. Response to the antifolate methotrexate (MTX) may be modified in 677TT individuals because MTHFR converts nonmethylated folates, used for thymidine and purine synthesis, to 5-methyltetrahydrofolate, used in homocysteine remethylation to methionine. To study potential interactions between MTHFR activity and MTX, we examined the impact of decreased and increased MTHFR expression on MTX response in mice.