基因多态性对宜昌地区类风湿关节炎患者甲氨蝶呤疗效的影响

目的探讨甲基四氢叶酸还原酶(MTHFR)和ATP结合盒转运蛋白1(ABCB1)等位基因在宜昌地区类风湿关节炎(RA)患者中分布情况,及其与甲氨蝶呤(MTX)治疗效果的相关性。方法收集整理2016年1月—2019年6月宜昌某三甲医院基因检测室进行MTHFR C677T、MTHFR A1298C、ABCB1 C3435T基因多态性检测的RA患者病例64例,回顾性分析相关基因型分布情况及基因多态性与疗效的影响。结果64例RA患者中MTHFR C677T基因位点CC、CT、TT型分布频率为46.88%,40.62%,12.50%;MTHFR A1298C基因位点AA、AC、CC型分布频率为78.13%,18.75%,3.12%;ABCB1 C3435T基因位点CC、CT、TT型分布频率为51.56%,34.38%,14.06%,均符合Hardy-Weinberg遗传平衡(P>0.05)。MTHFR C677T、MTHFR A1298C、ABCB1 C3435T基因多态性与药物疗效未观察到明显相关性。64例RA患者中至少发生一个基因位点改变为51例,基因突变率为79.69%,基因突变的发生可能影响红细胞沉降率、丙氨酸氨基转移酶的数值改变。结论相同地区同种疾病患者间基因多态性存在明显的个体差异,MTHFR、ABCB1基因多态性的改变可能与小剂量MTX的治疗效果或毒副反应有关。

Effect of Gene Polymorphism on the Therapeutic Effect of Methotrexate in Patients with Rheumatoid Arthritis in Yichang

Objective To investigate the distribution of MTHFR and ABCB1 alleles in patients with rheumatoid arthritis(RA)in Yichang and their relationship with MTX correlation.Methods A retrospective study was conducted to collect patients cases of RA detected by gene polymorphism of MTHFR 677 C>T,MTHFR 1298 A>C,ABCB13435 T>C,from January 2016 to June 2019 in the gene testing laboratory of a third-class hospital of Yichang.Retrospectively analyze the distribution of related genotypes and the impact of gene polymorphisms and curative effects.Results Among the 64 patients,MTHFR C677T CC,CT,TT type distribution frequency of 46.88%,40.62%,12.50%;MTHFR A1298C AA,AC,CC Distribution frequency of 78.13%,18.75%,3.12%;ABCB1 C3435T CC,CT,TT type distribution frequency of 51.56%,34.38%,14.06%,all of which were in line with Hardy-Weinberg genetic equilibrium(P>0.05).No significant correlation was observed between the drug efficacy and MTHFR C677T,MTHFR A1298C,ABCB1 C3435T gene polymorphisms.Among the 64 patients with RA,at least one gene locus was changed in 51 cases,with a gene mutation rate of 79.69%.The occurrence of gene mutation may affect the changes of ESR and ALT values.Conclusion There are obvious individual differences in genetic polymorphisms among patients with the same disease in the same region.The changes in MTHFR and ABCB1 gene polymorphisms may be related to the treatment effect or toxic side effects of low-dose MTX.