MTHFR和TS基因多态性与接受阿扎胞苷治疗的骨髓增生异常综合征患者预后的相关性

Correlation between MTHFR,TS genetic variants and prognosis in patients with myelodysplastic syndrome treated with azacytidine

目的:探究亚甲基四氢叶酸还原酶(MTHFR)和胸苷酸合成酶(TS)基因多态性与接受阿扎胞苷治疗的骨髓增生异常综合征(MDS)患者预后的相关性。方法:选取2018-02-2018-07在我院诊断及接受阿扎胞苷治疗的MDS患者93例,75 mg/m^2静脉滴注,qd。检测所有患者MTHFR和TS基因多态性,并进行18个月的随访,对比随访期内死亡和非死亡患者的基因分型,并使用Cox回归分析死亡的独立危险因素,分析上述基因突变对MDS患者预后的诊断效能。结果:MTHFR C677T中T的基因频率为46.38%,C1928A中C的基因频率为17.97%,TS(5’-UTR)中3R的基因频率为71.84%,TS(3’-UTR)中+6的基因频率为52.88%;死亡与未死亡患者在MTHFR C677T、TS(5’-UTR)、TS(3’-UTR)的基因分型存在显著差异(P<0.05);MTHFR C677T T/T、TS(3’-UTR)+6/+6突变型是死亡发生的独立危险因素(HR=9.510,6.906;P=0.002,0.004);MTHFR C677T T/T、TS(3’-UTR)+6/+6预测死亡的诊断效能无明显差异(P>0.05),两者联合诊断可有效提高诊断敏感性(P<0.05)。结论:MTHFR C677T T/T、TS(3’-UTR)+6/+6与接受阿扎胞苷治疗的MDS患者预后具有一定相关性,联合诊断具有更好的预测价值。

Objective:To explore the correlation between methylene tetrahydrofolate reductase(MTHFR),thymidylate synthase(TS) genetic variants and prognosis of myelodysplastic syndrome(MDS) patients treated with azacytidine.Method:From February 2018 to July 2018,93 patients diagnosed MDS in our hospital and treated with azacytidine were selected,azacytidine dose was 75 mg/m^2,iv,qd.MTHFR and TS genetic variants were detected in all patients,genotypes of dead and non-dead patients were compared during the follow-up period of 18 months.Cox regression analysis was used to analyze the independent risk factors of genotypes for death,and the diagnostic efficacy was analyzed.Result:The frequency of T in MTHFR C677 T was 46.38%,the frequency of C in MTHFR C1928 A was 17.97%,the frequency of 3 R in TS(5’-UTR) was 71.84%,the frequency of +6 in TS(3’-UTR) was 52.88%.There were significant differences in genotyping of MTHFR C677 T,TS(5’-UTR),TS(3’-UTR) between dead and non-dead patients(P<0.05).MTHFR C677 T T/T,TS(3’-UTR) +6/+6 were independent risk factors for death(HR=9.510,6.906;P=0.002,0.004).There was no significant difference in diagnostic efficacy(P>0.05),and the combined diagnosis could effectively improve the diagnostic sensitivity(P<0.05).Conclusion:There is significant correlation between MTHFR C677 T T/T,TS(3’-UTR) +6/+6 and prognosis of MDS patients treated with azacytidine,combined diagnosis has better predictive value.