Relationship between genetic variants in the adenosine pathway and outcome of methotrexate treatment in patients with recent-onset rheumatoid arthritis
- PMID: 16947783
- DOI: 10.1002/art.22032
Relationship between genetic variants in the adenosine pathway and outcome of methotrexate treatment in patients with recent-onset rheumatoid arthritis
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Objective: Among patients with rheumatoid arthritis (RA), there is a high degree of interindividual variability in the degree of response to methotrexate (MTX) treatment. This study was undertaken to explore polymorphisms in genes contributing to antiinflammatory adenosine release as novel predictors of MTX treatment outcome. VSports手机版.
Methods: In 205 patients with newly diagnosed RA, 5 polymorphisms in 5 genes coding for enzymes related to the release of adenosine were analyzed. All patients received standardized MTX treatment (up to 25 mg per week orally), combined with folic acid. MTX efficacy was evaluated by the Disease Activity Score (DAS) and compared among genotypes. The association between MTX-related adverse events and genotype was also assessed V体育安卓版. The following polymorphisms were determined: AMPD1 34C>T, ATIC 347C>G, ITPA 94C>A, MTR 2756A>G, and MTRR 66A>G. When significant differences were found by chi-square analysis, odds ratios (ORs) and 95% confidence intervals were calculated. .
Results: Patients carrying the AMPD1 34T allele, ATIC 347CC, or ITPA 94CC were more likely to have a good clinical response, as defined by a DAS of < or =2. 4 (OR [95% confidence interval] 2. 1 [1. 0-4. 5], 2. 5 [1. 3-4. 7], and 2. 7 [1. 1-8. 1], respectively). The likelihood of a good clinical response was increased if patients possessed all 3 favorable genotypes (OR 27. 8 [95% confidence interval 3. 2-250]). Regarding toxicity, only ATIC G allele carriers experienced a greater frequency of adverse events (OR 2 V体育ios版. 0 [95% confidence interval 1. 1-3. 7]). .
Conclusion: Polymorphisms in the AMPD1, ATIC, and ITPA genes are associated with good clinical response to MTX treatment. These findings indicate that genotyping may help in the identification of patients who will benefit most from MTX treatment and may assist clinicians in making treatment decisions regarding patients with recent-onset RA. VSports最新版本.
Comment in
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Do genetic variations in the adenosine pathway affect patient response to methotrexate? (V体育2025版)Nat Clin Pract Rheumatol. 2006 Dec;2(12):648-9. doi: 10.1038/ncprheum0353. Nat Clin Pract Rheumatol. 2006. PMID: 17133247 No abstract available.
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Effect of the 34C>T variant in the AMPD1 gene on the clinical response to methotrexate in patients with rheumatoid arthritis: comment on the article by Wessels et al. (V体育安卓版)Arthritis Rheum. 2007 Feb;56(2):694; author reply 694-5. doi: 10.1002/art.22397. Arthritis Rheum. 2007. PMID: 17265507 No abstract available.
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