Methotrexate effect on biochemical indices of psoriasis patients depends on MTHFR gene polymorphism

Abstract

Methotrexate (MTX) is the immunosuppressive anti-inflammatory drug and the antagonist of the enzyme dihydrofolate reductase. Pharmacogenomic studies and clinical evidences suggest that altered response to MTX in patients with different diseases is associated with polymorphisms of genes that regulate folate metabolism. The purpose of the article was to analyze the methotrexate effect on the biochemical indices of psoriasis patients depending on methylenetetrahydrofolate reductase gene (MTHFR) polymorphisms. Effects of two single-nucleotide polymorphisms, C677T and A1298C, were studied. An increase of alanine aminotransferase and aspartate aminotransferase activity above the normal level in the patients with both MTHFR gene polymorphisms after methotrexate intake was observed. In patients with CC, TT, CT genotypes for C677T polymorphism and AA genotype for A1298C polymorphism of MTHFR gene, significant differen­ces in alpha-amylase activity before and after treatment with methotrexate were detected. Analysis of the biochemical indices of patients with arthropathic and vulgaris psoriasis showed that the positive effect of MTX treatment could be associated with wild-type alleles in both polymorphisms of MTHFR gene, while the ineffectiveness of methotrexate was associated with the dihеterozygous genotype. The largest number of smokers was found within the CTAA genotype group (37.5%), while no smokers were observed within TTAA patients and most of CCAA patients. The data obtained testify the utility of the individual approach to the psoriasis patients therapy taking into account genetic background.

Keywords

• a1298c
• c677t
• folate cycle
• methotrexate
• mthfr gene
• psoriasis
• single-nucleotide polymorphism (snp)
• smoking