The aim of the study was to look for the association of FPGS 2752 G > A (rs1544105), FPGS 1994 A > G (rs10106), and GGH 452 C > T (rs 11545078), GGH −401C > T (rs 3758149) gene polymorphisms with methotrexate (MTX) treatment response and MTX-induced adverse events in South Indian Tamil patients with rheumatoid arthritis (RA). Further the influence of these gene polymorphisms on MTX polyglutamate levels was analyzed. A total of 330 patients with RA were investigated. FPGS gene polymorphisms were analyzed by TaqMan 5ʹnuclease assay and GGH gene polymorphisms were analyzed by PCR-RFLP. Methotrexate polyglutamates (nmol/L of packed erythrocytes) were measured by liquid chromatography mass spectrometry (LCMS/MS) method. We found that the heterozygous genotype of FPGS rs1544105 [p = 0.02, OR 1.93, 95% CI (1.15–3.35)] and FPGS rs10106 AG genotype [p = 0.01, OR 2.11, 95% CI (1.20–3.71)] were associated with MTX adverse events. FPGS rs1544105 and GGH −401C > T SNPs influenced the polyglutamate levels. None of the investigated SNPs seems to be associated with MTX treatment outcome.

该研究的目的是寻找FPGS 2752 G> A（rs1544105），FPGS 1994 A> G（rs10106）和GGH 452 C> T（rs 11545078），GGH −401C> T（rs 3758149）的关联氨甲蝶呤（MTX）治疗反应和MTX引起的南印度泰米尔类风湿性关节炎（RA）患者的不良反应的基因多态性。进一步分析了这些基因多态性对MTX多谷氨酸水平的影响。共调查了330例RA患者。通过TaqMan 5ʹ核酸酶分析和GGH分析FPGS基因多态性通过PCR-RFLP分析基因多态性。通过液相色谱质谱法（LCMS / MS）测量甲氨蝶呤多谷氨酸盐（nmol / L填充红细胞）。我们发现FPGS rs1544105的杂合基因型[ p  = 0.02，或1.93，95％CI（1.15-3.35）]和FPGS rs10106 AG基因型[ p  = 0.01，或2.11，95％CI（1.20-3.71）]相关与MTX不良事件有关。FPGS rs1544105和GGH -401C> T SNP影响多聚谷氨酸水平。研究的SNPs似乎都与MTX治疗结果无关。