The impact of C677T and A1298C MTHFR polymorphisms on methotrexate therapeutic response in East Bohemian region rheumatoid arthritis patients
Language English Country Germany Media print-electronic
Document type Journal Article, Research Support, Non-U.S. Gov't
- MeSH
- Antirheumatic Agents adverse effects metabolism therapeutic use MeSH
- Adult MeSH
- Pharmacogenetics MeSH
- Phenotype MeSH
- Heterozygote MeSH
- Homozygote MeSH
- Polymorphism, Single Nucleotide * MeSH
- Middle Aged MeSH
- Humans MeSH
- Linear Models MeSH
- Logistic Models MeSH
- Methotrexate adverse effects metabolism therapeutic use MeSH
- Methylenetetrahydrofolate Reductase (NADPH2) genetics metabolism MeSH
- Odds Ratio MeSH
- Polymerase Chain Reaction MeSH
- Prospective Studies MeSH
- Cross-Sectional Studies MeSH
- Retrospective Studies MeSH
- Arthritis, Rheumatoid diagnosis drug therapy enzymology genetics MeSH
- Risk Factors MeSH
- Aged, 80 and over MeSH
- Aged MeSH
- Treatment Outcome MeSH
- Check Tag
- Adult MeSH
- Middle Aged MeSH
- Humans MeSH
- Male MeSH
- Aged, 80 and over MeSH
- Aged MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Geographicals
- Czech Republic MeSH
- Names of Substances
- Antirheumatic Agents MeSH
- Methotrexate MeSH
- Methylenetetrahydrofolate Reductase (NADPH2) MeSH
- MTHFR protein, human MeSH Browser
Some single-nucleotide polymorphisms (SNPs) might be predictive of methotrexate (MTX) therapeutic outcome in rheumatoid arthritis (RA). The aim of this study was to determine whether SNPs in the methylenetetrahydrofolate reductase (MTHFR) gene are predictive of MTX response. Comparison was made using EULAR response criteria and according to the change of DAS28 (∆DAS28) after a 6-month MTX treatment in RA patient cohort. The two SNPs C677T (rs1801133) and A1298C (rs1801131) have been genotyped. A total of 120 patients were enrolled in the study, and all of them fulfilled the American College of Rheumatology 1987 RA criteria and are currently or previously taking MTX oral treatment, either as a monotherapy (n = 65) or in a combination with other disease-modifying antirheumatic drugs (n = 55). Genotyping was performed using qPCR allelic discrimination. We did not found any association of C677T and A1298C genotypes with MTX treatment inefficacy in dominant model (OR 1.23, 95 % CI 0.57-2.65, P = 0.697; and OR 0.98, 95 % CI 0.47-2.14, P = 1.0, respectively), or in recessive and codominant models. However, when ∆DAS28 after a 6-month therapy was used as a measure of treatment efficacy, the 677CT and 1298AC genotypes were found to be significantly associated with less favorable response to MTX (P = 0.025 and P = 0.043, respectively). In addition, even lower ∆DAS28 was determined for double-mutated 677CT-1298AC heterozygotes. It means that a synergistic effect of 677CT and 1298AC genotypes was observed. Nevertheless, the DAS28 baseline was lower here comparing to other genotypes. Unexpectedly, quite the opposite trend-i.e., better response to MTX-was found in genotypes 677CC-1298CC and 677TT-1298AA. It is an intriguing finding, because these double-mutated homozygotes are known for their low MTHFR-specific activity. Global significance was P = 0.013, η (2) = 0.160-i.e., large-size effect. Thus, our data show greater ability of 677CC-1298CC and 677TT-1298AA genotypes to respond to MTX treatment.
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