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Analysis of association of ADORA[sub]2 A and ADORA[sub]3 polymorphisms genotypes/haplotypes with efficacy and toxicity of methotrexate in patients with rheumatoid arthritisGrk, Milka ...Adenosine receptors ADORA2A and ADORA3 are part of the adenosine-mediated antiinflammatory pathway and are overexpressed in patients with Rheumatoid arthritis (RA). Methotrexate (MTX) ... antiinflammatory effects are partially mediated via increased release of adenosine into extracellular space. Polymorphisms in ADORA2A and ADORA3 genes may have an impact on the efficacy and toxicity of MTX in RA patients. The study included 127 RA patients. Treatment efficacy was estimated using the changes in Disease activity score (DAS28) after 6 months of MTX monotherapy, according to EULAR response criteria. Patients with good and moderate response were classified as "responders", and with a poor response as "nonresponders". Adverse effects were collected during the follow-up period. Genotyping for polymorphisms within ADORA2A gene (rs2298383, rs2236624, rs5751876, rs17004921) and ADORA3 gene (rs2298191, rs1544223, rs3393) was performed using the KASPar assays. Among patients 112 (88.19%) were responders (18.8% good, 81.2% moderate). We observed no association between analyzed genotypes or alleles and MTX response by EULAR criteria but carriers of ADORA2A rs17004921 T allele (CT + TT) had a higher DAS28 decrease after 6 months of treatment than patients with CC genotype (p = 0.013). Adverse effects were reported in 31 patients (24.41%). Bone erosions were present in 82 (64.6%) patients. Haplotype block was observed among all 3 analyzed polymorphisms within ADORA3 gene and TAA haplotype was associated with bone erosions (29% vs 15.6%, p = 0.023) and hepatotoxicity (51.3% vs 21.6%, p = 0.013). According to our study, ADORA3 TAA haplotype may be associated with bone erosions and hepatotoxicity in RA patients treated with MTX.Source: Pharmacogenomics journal. - ISSN 1470-269X (Vol. 20, iss. 6, Dec. 2020, str. 784-791)Type of material - article, component part ; adult, seriousPublish date - 2020Language - englishCOBISS.SI-ID - 17030403
Author
Grk, Milka |
Milić, Vera |
Dolžan, Vita |
Maksimovic, Nela |
Damnjanovic, Tatjana |
Dusanovic Pjevic, Marija |
Pešić, Milica |
Novaković, Ivana |
Jekić, Biljana
Topics
rheumatoid arthritis |
methotrexate |
efficacy and toxicity |
revmatoidni artritis |
metotreksat |
učinkovitost in toksičnost
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Database name | Field | Year |
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Links to authors' personal bibliographies | Links to information on researchers in the SICRIS system |
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Grk, Milka | ![]() |
Milić, Vera | ![]() |
Dolžan, Vita | 11711 |
Maksimovic, Nela | ![]() |
Damnjanovic, Tatjana | ![]() |
Dusanovic Pjevic, Marija | ![]() |
Pešić, Milica | ![]() |
Novaković, Ivana | ![]() |
Jekić, Biljana | ![]() |
Source: Personal bibliographies
and: SICRIS
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