Effect of methotrexate on the survival of human lymphocyte cultures carrying MTHFR 677 (C>T) and MTHFR 1298 (A>C) mutations

Abstract

The correlations between the presence of MTHFR 677 (C>T) and MTHFR 1298 (A>C) mutations in human lymphocytes and the sensitivity of lymphocytes to methotrexate (MTX) were examined in cultures derived from 82 unrelated women, genotyped for these mutations by polymerase chain reaction–restriction fragment length polymorphism. Lymphocytes heterozygous for the mutant allele, MTHFR 677T, were significantly more sensitive to methotrexate than those carrying the homozygous wild-type allele, MTHFR677C, and those carrying either the mutant or the wild-type alleles in the polymorphic MTHFR 1298 site. In addition, the lymphocyte cultures carrying the mutant MTHFR 1298C allele were not different in their sensitivity to MTX from those cultures carrying the wild-type allele, MTHFR 1298A. This demonstrated that the polymorphic site MTHFR C677, but not MTHFR1298, could be considered as a useful pharmacogenetic determinant in planning and designing the effective personal MTX chemotherapeutic doses and regimes.

Keywords::

• MTHFR C677C>T
• MTHFR A1298A>C
• methotrexate
• human lymphocytes

Aknowledgment

This study was supported by grant number 2/2005 from the Deanship of Research and Higher Studies at Yarmouk University (Irbid, Jordan).

Declaration of interest: The authors report no conflicts of interest.