| Description |
Methotrexate (MTX) is a first-line disease-modifying antirheumatic drug (DMARD) for rheumatoid arthritis (RA), but individual variation in treatment response remains unexplained. The differences in drug efficacy and adverse drug reactions (ADRs) may be caused by genetic variations. We investigated the effect of single nucleotide polymorphisms (SNPs) in two genes encoding membrane-spanning proteins, namely, reduced folate carrier RFC/SLC (G>A (rs7499), A>G (rs2838956) and 180G>A (rs1051266)) and adenosine triphosphate binding cassette B1 (ABCB1, rs1045642). Tagged SNPs were genotyped in 162 patients with RA in China. Then, we analyzed the relationships between these SNPs and therapeutic outcomes related to MTX in Chinese RA patients. No significant association was found between the RFC/SLC (G>A (rs7499) and A>G (rs2838956)) and ABCB1 (rs1045642) gene polymorphisms and the response to MTX in RA patients. However, MTX-related toxicity was associated with one SNP, RFC rs1051266 AA vs GG (p=0.009, OR=6.523, 95% CI: 1.596, 26.565). SLC19A1 A>G rs2838956 showed a trend toward a significant association (p=0.085, OR=0.377, 95% CI: 0.124, 1.143) with toxicity. Our results suggest that the RFC 180G>A (rs1051266) SNP exerts a potentially protective effect against the risk of ADRs in Chinese RA patients treated with MTX. Further studies are required to validate these findings. |
