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目的探讨异柠檬酸脱氢酶1(IDH1)基因多态性对非洲人群急性白血病患者阿糖胞苷耐药性的影响。方法应用来自人类基因组计划(HapMap)非洲人群的细胞株培养后,给予不同浓度的阿糖胞苷(1、5、40、80μmol/L)共培养72 h。应用alamar Blue检测细胞存活曲线、阿糖胞苷的耐药性(以更高的阿糖胞苷曲线下面积表示)。梯形法计算阿糖胞苷曲线下面积,AUC进行Log2转换后统计分析。Taqman PCR法检测非洲人群IDH1基因多态性。结果非洲人群中,IDH1 rs10173938、rs10192397与阿糖胞苷更高的曲线下面积相关[rs10173938:AA比(AC+CC),P=0.040;rs10192397:(CC+CT)比TT,P=0.036)]。结论非洲人群急性白血病患者的阿糖胞苷耐药性受IDH1基因多态性影响。
Objective To investigate the effects of isocitrate dehydrogenase 1 (IDH1) gene polymorphism on cytarabine resistance in African patients with acute leukemia. Methods After the cell lines from human population of HapMap in Africa were cultured, different concentrations of cytarabine (1,5,40,80 μmol / L) were co-cultured for 72 h. Cell viability curves, cytarabine resistance (expressed as area under the higher cytarabine curve) were measured using alamar Blue. Trapezoidal method to calculate the area under the curve of cytarabine, AUC log2 conversion after statistical analysis. Taqman PCR Detection of IDH1 Gene Polymorphism in African Populations. Results In African populations, IDH1 rs10173938, rs10192397 correlated with higher area under the curve of cytarabine [rs10173938: AA ratio (AC + CC), P = 0.040; rs10192397: (CC + CT) vs TT, P = 0.036) ]. Conclusions Cytarabine resistance in patients with acute leukemia in African populations is affected by the IDH1 gene polymorphism.