类风湿关节炎患者亚甲基四氢叶酸还原酶基因多态性与甲氨蝶呤治疗的相关性研究

Correlation of methylene tetrahydrofolate reductase gene single necleotide polymorphisms and therapeutic effect of methotrexate in rheumatoid arthritis patients

目的探讨类风湿关节炎(RA)患者亚甲基四氢叶酸还原酶(MTHFR)基因rs1801133C/T、rs1801131A/C、rs2274976A/G单核苷酸多态性(SNP)在RA患者和健康人群分布情况,以及与甲氨蝶呤(MTX)治疗的相关性。方法收集皖籍汉族活动期RA患者110例,口服MTX 10～15mg/周,评价疗效及不良反应。180例皖籍汉族健康人群作为正常对照。采用实时荧光定量PCR法检测基因型。结果rs1801133C/T、rs1801131A/C、rs2274976A/G 3个位点多态性分布在皖籍汉族RA患者和正常对照组间差异无显著性。RA患者中MTX治疗有效组的rs1801131C等位基因频率高于治疗无效组(P<0.05)。有不良反应组中rs1801133T及rs2274976A等位基因频率高于无不良反应组(P<0.05)。结论rs1801133C/T、rs1801131A/C、rs2274976A/G多态性分布在皖籍汉族RA患者与正常人群之间差异无显著性。rs1801131A/C多态性与MTX的疗效相关。rs1801133C/T及rs2274976A/G多态性与MTX不良反应相关。

Objective To investigate the distribution of methylene tetrahydrofolate reductase（MTHFR） rs1801133C/T, rs1801131A/C,rs2274976A/G single necleotide polymorphisms（SNPs） in rheumatoid arthritis （RA） patients and the healthy control group,and to determine the association of methotrexate（MTX） treatment in RA patients.Methods 110 RA patients treated with the MTX（10～15 mg/week） and 180 healthy controls were involved in this study who were all the Chinese Han people from Anhui province.To investigate the MTX related clinical efficacy and adverse effects（AEs） in RA patients.The genotypes were detected by real-time fluorescent quantitative PCR.Results There was no significant difference in allele frequencies of the three SNPs between RA group and the control group.Among the RA patients,the allele frequency of rs1801131C in the effective group was higher than that in the ineffective group（P0.05）.The allele frequency of rs1801133T and rs2274976A were both higher in the group with AEs than that in the group without AEs（P0.05）.Conclusion There is no significant difference in the distribution of the three SNPs between RA group and control group.The rs1801131A/C may be associated with MTX clinical efficacy in RA patients.The rs1801133C/T and rs2274976A/G may be associated with MTX related AEs.