亚甲基四氢叶酸还原酶基因多态性对小剂量甲氨喋呤治疗类风湿关节炎不良反应的影响  

Relationship between single nucleotide polymorphism of methylenetetrahydrofolate reductase gene and the side effect of low-dose methotrexate in the treatment of rheumatoid arthritis

作　　者：石宇红[1] 周润华[1] 许佳[1] 朱芳晓[1] 李宝贞[1] 李丽梅[1] 莫汉有[1] 

机构地区：[1]桂林医学院附属医院风湿免疫科,广西541002

出　　处：《中国临床新医学》2013年第3期211-214,共4页CHINESE JOURNAL OF NEW CLINICAL MEDICINE

基　　金：广西卫生厅科研课题(编号:Z2009044);桂林市科学研究与技术开发项目(编号:20090538)

摘　　要：目的探讨亚甲基四氢叶酸还原酶(MTHFR)基因C677T多态性对小剂量甲氨喋呤(MTX)治疗类风湿关节炎的影响。方法收集类风湿关节炎患者治疗前及治疗后0,12,24及48 w的临床表现及实验室指标和不良反应信息,评估疗效。采用实时荧光定量聚合酶链反应(FQ-PCR)方法测定类风湿关节炎患者183例(RA组)及健康对照组100例的MTHFR基因C677T多态性,比较两组间基因型分布及等位基因频率。结果 C677T基因型分布在RA组与健康对照组间差异无统计学意义(P>0.05);C677T各基因型在MTX治疗有效率差异无统计学意义(P>0.05)。TT基因型组肝毒性及血液系统不良反应的发生率明显高于CC基因型组,差异均有统计学意义(P<0.05)。结论 MTHFR基因C677T多态性与RA发病和MTX疗效无关,但与MTX治疗后血液系统不良反应、肝毒性有关联。Objective To investigate single nucleotide polymorhtism of methylenetetrahydrofolate（MTHFR） reductase gene and its association with the side effect of methotrexate in the treatment of rheumatoid arthritis（RA）.Methods The clinical and laboratory data of 183 patients with RA were evaluated before treatment and at 0,12,24,48 weeks after treatment.Efficacy and side effects of 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 frenquency of 6777CC,CT,TT between RA patients and the healthy controls（P＆gt;0.05）.There was no significant difference in the frenquency of 6777CC,CT,TT between the group in which MTX was effective and the other groups in which MTX was not effective（P＆gt;0.05）.There was significant difference in the frenquency of 6777CC,CT,TT between the group with MTX related adverse effects and group without MTX related adverse effects.The occurrence rate of side effects of MTX in the patients with 677TT was higher than those without mutation（CC）（P＆lt;0.05）.Conclusion There is no relationship between the pathogenesis of RA and the C677T mutation of MTHFR gene.MTHFR gene C677T mutation is probably one of genetic risk factors for the sidde effects of MTX,such as hepatic toxicity and adverse reactions of the blood system.

关 键 词：类风湿关节炎 亚甲基四氢叶酸还原酶基因 单核苷酸多态性 甲氨喋呤 不良反应 

分 类 号：R593.2[医药卫生—内科学]