Target Gene Polymorphisms and Clinical Response to Methotrexate in Chinese Rheumatoid Arthritis Patients

This study aimed to evaluate the associations between genetic polymorphisms within target genes and clinical response to methotrexate (MTX) in Chinese rheumatoid arthritis (RA) patients.

One hundred and fifteen RA patients treated with MTX for approximately 3 months were enrolled, and clinical response was determined by European League Against Rheumatism (EULAR) response criteria and disease activity score in 28 joint counts - erythrocyte sedimentation rate (DAS28-ESR) low disease activity (LDA). Thirty genetic polymorphisms within DHFR, TYMS, ATIC, ADA, and AMPD1 were genotyped.

The major allele of ATIC rs2372536 (RR = 0.85, 95% CI = 0.72 - 0.99, p = 0.04), ATIC rs4673991 (RR = 0.85, 95% CI = 0.73 - 0.99, p = 0.04), ATIC rs4673993 (RR = 0.85, 95% CI = 0.73 - 0.99, p = 0.04), ADA rs2057638 (RR = 0.86, 95% CI = 0.76 - 0.99, p = 0.03), and ADA rs6017375 (RR = 0.86, 95% CI = 0.76 - 0.99, p = 0.03) were found to be significantly associated with EULAR response under dominant model, while the major allele of ADA rs371927 (RR = 1.23, 95% CI = 1.04 - 1.46, p = 0.02) was shown to be significantly associated with EULAR re¬sponse under recessive model. Moreover, the major allele of ADA rs1799880 (RR = 0.60, 95% CI = 0.43 - 0.84, p = 0.003) and rs6031697 (RR = 0.61, 95% CI = 0.47 - 0.78, p < 0.001) were detected to be significantly associated with DAS28-ESR LDA.

Genetic polymorphisms within ATIC and ADA were significantly associated with clinical response to MTX in Chinese patients with RA.