Effect of methotrexate on the survival of human lymphocyte cultures carrying MTHFR 677 (C>T) and MTHFR 1298 (A>C) mutations.
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.
Al-Refai
Ekhlas A
EA
Department of Biological Sciences, Faculty of Science, Yarmouk University, Irbid, Jordan.
Sadiq
May F
MF
Khassawneh
Mohammad Y
MY
Amjad D
Al-Nasser
AN
D000483:Alleles; D018501:Antirheumatic Agents / Q000494:pharmacology; D015198:Designer Drugs / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D004358:Drug Therapy / Q000379:methods; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008214:Lymphocytes / Q000187:drug effects* / Q000502:physiology; D008727:Methotrexate / Q000494:pharmacology*; D042965:Methylenetetrahydrofolate Reductase (NADPH2) / Q000235:genetics*; D009154:Mutation; D010597:Pharmacogenetics; D011110:Polymorphism, Genetic; D020641:Polymorphism, Single Nucleotide; D012680:Sensitivity and Specificity; D014407:Tumor Cells, Cultured
D018501:Antirheumatic Agents; D015198:Designer Drugs; D042965:Methylenetetrahydrofolate Reductase (NADPH2); D008727:Methotrexate