rs7499

This pilot study investigated associations between genetic polymorphisms in transporter genes (SLC19A1, ABCC2, ABCB1, ABCC1, ABCC3, ABCG2) and clinical response to methotrexate (MTX) in 100 Chinese rheumatoid arthritis (RA) patients. Multiple SNPs showed significant associations with MTX response: SLC19A1 rs12659 and rs3788200 major alleles were associated with EULAR good/moderate response (RR=1.42-1.45, p=0.03-0.04); ABCC2 rs3740066 major allele was associated with DAS28-ESR low disease activity (RR=0.67, p=0.02). Haplotype analysis identified significant associations of SLC19A1 and ABCC2 haplotypes with clinical response outcomes.

This pharmacogenetics study analyzed 28 SNPs in methotrexate (MTX) metabolism genes (SLC19A1/RFC1, ABCB1, FPGS, GGH) in two Spanish populations with rheumatoid arthritis (n=124 and n=194). Key findings: FPGS rs10987742 and rs10106 associated with MTX response (p=0.033, p=0.041); FPGS rs10106 also associated with MTX survival (p=0.005) and toxicity (p=0.021); ABCB1 rs868755, rs10280623, rs1858923 associated with toxicity (p=0.025, p=0.048, p=0.031). In the first study, MTHFR rs17421511 (p=0.024) and rs1476413 (p=0.0086) associated with response, DHFR rs1643650 (p=0.026) associated with response, ATIC rs16853826 associated with toxicity (p=0.039).