Polymorphisms within the adenosine receptor 2a gene are associated with adverse events in RA patients treated with MTX.
OBJECTIVE
To examine the role of adenosine receptor 2a gene (ADORA2a) polymorphisms on outcome of MTX treatment in RA.


METHODS
Subjects included 309 RA patients with a defined response to MTX. Patients were included if they were (i) good responders (n = 147) (ESR <20 for >6/12 on stable dose of MTX) (ii) inefficacy failures (n = 101) (physician statement and failure to reduce ESR/CRP by 20%) or (iii) adverse event (AE) failures (n = 61) (verified by medical record review). AEs were sub-divided into gastrointestinal (GI) (n = 24), abnormal LFTs (n = 20) or other (n = 17). 8 single nucleotide polymorphisms (SNPs) within ADORA2a were genotyped using the Sequenom MALDI-TOF platform.


RESULTS
Five SNPs within ADORA2a were associated with stopping MTX for AEs (OR 2.1-3.07, P < 0.05 for all). Analysis by AE type showed that the association was specific for GI toxicity. No association was observed between ADORA2a and inefficacy outcomes.


CONCLUSIONS
Genetic variation within ADORA2a is significantly associated with AEs on MTX, specifically GI AEs. Knowledge of the ADORA2a genotype may help to improve identification of patients at high risk of GI toxicity with MTX.
ARC Epidemiology Unit, University of Manchester, UK.
S L
SL
Hider
W
W
Thomson
L F
LF
Mack
D J
DJ
Armstrong
M
M
Shadforth
I N
IN
Bruce
D000328:Adult; D000368:Aged; D018501:Antirheumatic Agents / Q000009:adverse effects* / Q000627:therapeutic use; D001172:Arthritis, Rheumatoid / Q000188:drug therapy / Q000235:genetics*; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006801:Humans; D007166:Immunosuppressive Agents / Q000009:adverse effects / Q000627:therapeutic use; D008727:Methotrexate / Q000009:adverse effects* / Q000627:therapeutic use; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D043683:Receptors, Adenosine A2 / Q000235:genetics*; D012189:Retrospective Studies; D016896:Treatment Outcome
D018501:Antirheumatic Agents; D007166:Immunosuppressive Agents; D043683:Receptors, Adenosine A2; D008727:Methotrexate