Abstract | BACKGROUND:
Methotrexate is the most frequently administered first-line treatment for rheumatoid arthritis (RA). The disease-modifying effects of methotrexate are mainly associated with enhanced release of free adenosine. The downstream anti-inflammatory effects of adenosine are mediated via its binding to adenosine receptor 2A (ADORA2A) and 3 (ADORA3). Many clinically important single nucleotide polymorphisms (SNPs) were reported in ADORA2A and ADORA3 genes. OBJECTIVES: To investigate whether tagging ADORA2A and ADORA3 polymorphisms influences methotrexate treatment in RA. METHODS: In total, 212 RA patients treated with methotrexate were genotyped for tagging ADORA2A (rs2298383, rs8141793, rs2236624, rs5751876, rs35320474, and rs17004921) and ADORA3 SNPs (rs2298191, rs1544223, rs78594984, rs35511654, rs2229155, rs3393, and rs3394). RESULTS: RA patients who carried ADORA3 rs35511654 G allele showed a tendency toward better response to methotrexate treatment (P = 0.054). Carriers of ADORA2A polymorphic allele rs2298383 (P = 0.011), rs2236624 (P = 0.027), rs5751876 (P = 0.018), and rs35320474 (P = 0.026) were less likely to experience methotrexate induced adverse events. All associations remained significant after adjustment for clinical factors. The effects of these polymorphisms were also significant in haplotype analyses. CONCLUSIONS:
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Authors | Nadja Kobold, Barbara Jenko, Matija Tomšič, Vita Dolžan, Sonja Praprotnik |
Journal | The Israel Medical Association journal : IMAJ
(Isr Med Assoc J)
Vol. 21
Issue 5
Pg. 333-338
(May 2019)
ISSN: 1565-1088 [Print] Israel |
PMID | 31140226
(Publication Type: Journal Article)
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Chemical References |
- ADORA2A protein, human
- ADORA3 protein, human
- Antirheumatic Agents
- Receptor, Adenosine A2A
- Receptor, Adenosine A3
- Methotrexate
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Topics |
- Antirheumatic Agents
(administration & dosage, adverse effects)
- Arthritis, Rheumatoid
(drug therapy, genetics)
- Drug Monitoring
(methods)
- Female
- Humans
- Male
- Methotrexate
(administration & dosage, adverse effects)
- Middle Aged
- Pharmacogenomic Testing
- Pharmacogenomic Variants
- Pharmacovigilance
- Polymorphism, Single Nucleotide
- Receptor, Adenosine A2A
(genetics)
- Receptor, Adenosine A3
(genetics)
- Slovenia
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