类风湿关节炎亚甲基四氢叶酸还原酶基因多态性与甲氨蝶呤疗效和不良反应的关系

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677CDT[rs1801133)、1298A/C(rs1801131)单核苷酸多态性(SNP)及其与甲氨蝶呤(MTX)治疗的疗效和不良反应相关性.方法 收集RA患者184例.分为单用MTX组、MTX联用其他改善病情抗风湿药(DMARD)组、非MTX的DMARD组,于治疗前及治疗后24周检查临床及实验室指标,评价疗效及不良反应.采用实时荧光定量聚合酶链反应(FQ-PCR)方法检测RA患者及100名健康对照组的MTHFR基因677C/T及1298A/C多态性,比较两组间基因型分布及等位基因频率.结果 677CC/CT/TT基因型分布在RA组(19%、67%、14%)与健康对照组(27%、56%、17%)基因型分布频率差异无统计学意义(P>0.05);1298AA/AC/CC基因型分布在RA组(66%、31%、3%)健康对照组(70%、30%、0%)基因型分布频率差异无统计学意义(P>0.05).677CC/CT/TT基因型分布在RA有心血管并发症组(6%、75%、19%)与正常对照组(27%、56%、17%)差异有统计学意义(P<0.05).在单用MTX治疗者巾,1298AA/AC/CC在MTX治疗有效组(54%、44%、2%)和无效组(90%、10%、O%)中差异有统计学意义(P<0.05),677CC/CT/TT在MTX有不良反应组(13%、71%、16%)和无不良反应组(48%、48%、4%)中差异有统计学意义(P<0.05).在MTX联用其他DMARD组,677CC/CT/TT在有不良反应组(9%、78%、13%)和无不良反应组(35%、50%、15%)中差异有统计学意义(P<0.05).结论 MTHFR基因677C/T及1298A/C多态性与RA发病无关;677 C/T多态性与RA心血管并发症的出现有关、与MTX治疗后的不良反应相关,1298 A/C多态性与MTX的疗效相关.

Relationship between the single nucleotide polymorphism of 5, 1O-methylenetetrahydrofolate reductase gene and the treatment of methotrexate in rheumatoid arthritis

Objective To investigate the single nucleotide polymorphism of 5,10-methylenetetrahy-drofolate reduetase gene and its association with the treatment of methotrexate in rheumatoid arthritis (RA).Methods A total of 184 patients with RA were divided into methotrexate (MTX) treatment group, MTX+other DMARDs treatment group, and treatment with other DMARDs but not MTX group. The clinical and laboratory data were evaluated before treatment and 24 weeks later. Efficacy and toxieities of each medication were also analyzed. Real-time fluorescent quantitative PCR was conducted to test gene mutations in RA patients and 100 healthy controls. Results There was no significant difference in the frenqueney of 677CC,CT, "IT and 1298AA, AC, CC between RA patients and the healthy controls. There was significant difference in the frenqueney of 677CC, CT, Tr between RA patients with cardiovascular eomplieations and the healthy controls. In the MTX treatment group, there was significant difference in the frenqueney of 1298AC, CC between the group in which MTX was effective and the other groups in which MTX was not effective, the occurrence rate of side effects of MTX in the patients with 677TT was higher than those without mutation(CC).In MTX+other DMARDs group, the occurrence rate of side effects of MTX in the patients with 677TT and CT was higher than that without mutation (CC). Conclusion There is no relationship between the pathogenesis of RA and the 677C/T, 1298A/C mutation of MTHFR gene. MTHFR gene 677C/T mutation is probably one of the genetic risk factors for cardiovascular complications of RA patients and the side effects of MTX. MTHFR gene 1298A/C allel is associated with the efficacy of MTX.