银屑病亚甲基四氢叶酸还原酶基因多态性与甲氨蝶呤疗效及不良反应的关系

Relationship between the Single Nucleotide Polymorphism of 5,10 Methylene Tetrahydrofolate Reductase Gene with the Efficacy and Adverse Effect of Methotrexate in Psoriasis

目的:探讨银屑病患者亚甲基四氢叶酸还原酶(MTHFR)基因C677C/T多态性及其与长期小剂量甲氨蝶呤(MTX)方案治疗的疗效和不良反应的相关性。方法:运用聚合酶链反应和限制性片段长度多态性分析(PCR-RFLP)的方法检测120例寻常型银屑病患者及100名健康对照组的MTHFRC677C/T多态性,比较两组间基因型及等位基因频率分布。在MTX治疗用药前,治疗后1、2、4、12周定期检查实验室指标,评价疗效及不良反应。结果:银屑病组MTHFR基因CC、CT、TT基因型分布分别为54.17%、32.50%、13.33%,与健康对照组(分别为43.00%、45.00%、12.00%)比较,差异无统计学意义(2=3.70,P>0.05)。有105例银屑病患者纳入疗效评估,各基因型间的疗效比较差异无统计学意义(2=1.45,P>0.05)。35.00%(42/120)患者出现不良反应,将有、无不良反应的两组基因型进行比较,差异有统计学意义(2=17.26,P<0.05),CT+TT基因型占不良反应组的71.43%,与无不良反应组(32.05%)比较差异有统计学意义(2=17.05,P<0.05)。29.17%(35/120)出现肝毒反应,将肝毒性组和无不良反应两组基因型分布比较差异有统计学意义(2=10.02,P<0.05),肝毒性组T等位基因出现频率较无不良反应组高,差异有统计学意义(2=7.52,P<0.05)。结论:MTHFR基因C677C/T多态性与银屑病的发病和MTX疗效无关,但与MTX治疗后的不良反应和肝毒性有关,T突变基因是不良反应的高危因素。

To investigate the single nucleotide polymorphism of 5,10 methylenetet-rahydrofolate reductase （ MTHFR） gene in psoriatic patients, and its association with the efficacy and adverse effect of the long term therapy of low-dose methotrexate （ MTX） .Methods：MTHFR gene was performed by the polymerase chain reaction-restriction fragment length polymorphism （ PCR-RFLP） in 120 patients and 100 heaIthy controIs.The clinical and laboratory data of 120 psoriatic patients were evaluated before treatment and at 1, 2, 4, 12 weeks after therapy.Efficacy and adverse effects of medication were analyzed.Results：There was no significant difference in the frenquency of MTHFR 677 CC, CT, TT between the psoriatic patients（54.17%,32.50%、13.33%） and the healthy controls（43.00%, 45.00%, 12.00%） （χ2 =3.70,P＆gt;0.05）.The therapeutic effect of MTX in 105 patients were evaluated, there was no significant difference a-mong different gene type groups（χ2=1.45,P〉0.05）.There were 42 cases （42/120, 35.00%） presented with MTX related adverse effects.A significant difference in the frequency of 677 CC, CT, TT was found between the group with adverse effects and the group without adverse effects（χ2=17.26,P〈0.05） , with a higher percentage of CT and TT gene type in the adverse effects group than that in the group without adverse effects（χ2=17.05,P〈0.05）.Also, there was a signifi-cant difference between the group with adverse reaction of hepatic toxicity and the group without adverse effects（χ2=10.02,P〈0.05）, with a higher frequency of T mutant gene in the hepatic toxicity group than that in the group without hepatic toxicity（χ2=7.52,P〈0.05）.Conclusion：There was no relationship between the pathogenesis of psoriasis and the efficacy of MTX with the mutation of MTHFR gene 677C/T.However, MTHFR gene C677T mutation was probably one of genetic risk factors for the adverse effects of MTX such as hepatic toxicity.T mutant gene was the risk factor of the adverse effects of MTX.