Associations Between Genetic Polymorphisms Within Transporter Genes and Clinical Response to Methotrexate in Chinese Rheumatoid Arthritis Patients: A Pilot Study

To investigate the associations between genetic polymorphisms within transporter genes and clinical response to methotrexate (MTX) in Chinese rheumatoid arthritis (RA) patients. A total of 100 RA patients receiving MTX were prospectively followed up for approximately 3 months to determine the clinical response based on several criteria, including European League Against Rheumatism (EULAR) good and moderate response, disease activity score in 28 joint counts - erythrocyte sedimentation rate (DAS28-ESR) low disease activity (LDA), change in DAS28-ESR (ΔDAS28-ESR) and ΔDAS28-ESR >0.6. Fifty-four single nucleotide polymorphisms (SNPs) within seven transporter genes, including and , were genotyped. Multivariable analysis revealed that rs12659 and rs3788200, rs3740066, rs4148396 and rs717620 were significantly associated with EULAR good and moderate response, and rs3740066 and rs717620 were significantly associated with DAS28-ESR LDA, and rs1128503, rs4148737 and rs2277624, rs4148416 were significantly associated with ΔDAS28-ESR. Moreover, 12 genetic polymorphisms were found to be significantly associated with ΔDAS28-ESR >0.6. With adjustment for corresponding confounders, TGAA haplotype consisting of rs1051266, rs1131596, rs12659 and rs3788200 was significantly associated with EULAR good and moderate response and ΔDAS28-ESR >0.6 compared with the most common haplotype CAGG. The haplotype TTT composed of rs717620, rs4148396 and rs3740066 was significantly associated with EULAR good and moderate response and ΔDAS28-ESR >0.6 compared with the most common haplotype CCC. Our results highlight the potential of genetic polymorphisms within transporter genes, particularly and , as predictors of clinical response to MTX in Chinese RA patients.