PHARMACOGENETIC EFFECTS OF METHOTREXATE (MTX) IN UKRAINIAN PATIENTS DEPENDING ON THE MTHFR GENOTYPES (CLINICAL CASES)

Georgian Med News. 2018 Jun:(279):111-117.

Abstract

The aim of the study is an evaluation the influence of MTHFR gene polymorphisms in the response to MTX in Ukrainian patients. The study group included unrelated Ukrainian patients with dermatoses - psoriasis vulgaris, psoriasis arthritis, psoriasis erythrodermic, atopic dermatitis, scleroderma, eczema, flat lichen and ectopic pregnancy. The materials for this study are based on the accumulated data from clinical observations of different reactions of patients with dermatoses and ectopic pregnancies when using methotrexate as the basic therapy according protocols. The analysis of the results obtained in the retrospective study indicated that MTX-treated patients had shown a different parameters depending on genotypes or haplotypes of MTHFR gene. After the treatment in the group of patients, carriers of CC genotype on C677T polymorphism of MTHFR gene, who received methotrexate, the normal levels of transaminases were observed. Probably, patients with the CCAA genotype are the fast metabolizers and could take methotrexate and other medications without complications for a long time. In the presented study, alpha-amylase levels in patients with CC and CT genotypes of C677T MTHFR gene before MTX treatment were normal or lower than normal. We found out that the level of amylase was significantly, almost 2 times, increased after treatment with MTX in patients with CCAA haplotype of MTHFR gene. Thus, the study of the association of polymorphisms of the MTHFR gene with a response to MTX has shown that the decrease in the therapeutic effect and the appearance of side effects in different genotypes is in the following relationship: CCAA <CTAA <CTAC. The main idea of future research is the search for ways to increase the effectiveness of therapy in patients, taking into account the pathophysiological processes and the genotypes of one-carbon metabolism genes for successful treatment.

MeSH terms

  • Adult
  • Dermatitis, Atopic / drug therapy
  • Dermatitis, Atopic / genetics
  • Female
  • Genotype
  • Humans
  • Male
  • Methotrexate / pharmacology*
  • Methotrexate / therapeutic use
  • Methylenetetrahydrofolate Reductase (NADPH2) / genetics*
  • Middle Aged
  • Pharmacogenetics
  • Polymorphism, Genetic
  • Pregnancy
  • Pregnancy, Ectopic / drug therapy
  • Psoriasis / drug therapy
  • Psoriasis / genetics
  • Ukraine
  • Young Adult

Substances

  • MTHFR protein, human
  • Methylenetetrahydrofolate Reductase (NADPH2)
  • Methotrexate