SLCO1B1基因多态性与类风湿关节炎患者多聚谷氨酸化甲氨蝶呤浓度及疗效的关系

Correlation of SLCO1B1 gene polymorphism with the concentration and therapeutic effects of methotrexate polyglutamates on rheumatoid arthritis

目的:研究SLCO1B1388A>G和521T>C基因多态性与类风湿关节炎(rheumatoid arthritis,RA)患者服用小剂量甲氨蝶呤治疗后红细胞中多聚谷氨酸化甲氨蝶呤(methotrexate polyglutamates,MTXPGs)浓度、疗效及肝毒性的关系。方法:前瞻性收集接受小剂量甲氨蝶呤治疗的137例RA患者,采用基因芯片法检测SLCO1B1基因,经HPLC-MS/MS法检测患者红细胞中MTXPGs浓度,应用SPSS软件分析SLCO1B1基因多态性与MTXPGs浓度、疗效及肝毒性的关系。结果:G、C等位基因的频率分别为73.7%、11.7%,SLCO1B1基因型分布符合Hardy-Weinberg平衡检测。388A>G和521T>C突变组与野生组间红细胞中MTXPGs浓度在患者服药第8,12,24,40周后差异均无统计学意义(P>0.05),同时不同基因型患者间疗效与肝毒性差异亦无统计学意义(P>0.05)。结论:SLCO1B1388A>G和521T>C基因多态性与MTXPGs浓度、疗效及肝毒性可能无关。

OBJECTIVE To study the relationship between SLCO1B1388A>G and 521T>C gene polymorphisms and the concentration,efficacy and hepatotoxicity of methotrexate polyglutamates(MTXPGs)in red blood cells of patients with rheumatoid arthritis(RA)after low-dose methotrexate treatment.METHODS A total of 137 RA patients treated with low-dose methotrexate were prospectively collected.The SLCO1B1 gene was detected by the gene chip method,and the MTXPGs concentration in erythrocytes was detected by HPLC-MS/MS method.The relationship between SLCO1B1 gene polymorphism and the MTXPGs concentration,therapeutic effects,as well as hepatotoxicity was analyzed by SPSS software.RESULTS The frequencies of G and C alleles were 73.7%and 11.7%,respectively.The distribution of SLCO1B1 genotype was in Hardy-Weinberg equilibrium.The MTXPGs concentrations in erythrocytes between the 388A>G and 521T>C mutation groups and their wild groups were not statistically different at 8,12,24,and 40 weeks(P>0.05),and there was no significant difference in efficacy and hepatotoxicity among different genotypes(P>0.05).CONCLUSION SLCO1B1388A>G and 521T>C gene polymorphisms may not be associated with MTXPGs concentrations,therapeutic effects or hepatotoxicity.