异柠檬酸脱氢酶1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

Influence of genetic variants of isocitrate dehydrogenase 1 on cytarabine resistance on African population with acute myeloid leukemia

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 explore the influence of gene polymorphism of isocitrate dehydrogenasel （IDH1） on cytarabine （ara-C） resistance on African population with acute myeloid leukemia. Methods Cell lines from international HapMap project panels with African ancestry were cultured and exposure to araC in different concentration （1, 5, 40, 80 μmol/L） for 72 h. Percent cell survival values and resistance of araC depicted by the area under the survival curve （AUC） were determined by alamar Blue. The AUC of araC was calculated using the trapezoidal rule and AUC values were Log2 transformed before statistical analysis. IDH1 genetic variants of African population were identified with Taqman PCR. Results IDH1 rs10173938, rs10192397 were significantly associated with high AUC of araC [rs10173938： AA vs （AC＋CC）, P = 0.040; rs10192397： （CC＋ CT） vs TY, P = 0.036]. Conclusion Cytarabine resistance in African population with acute myeloid leukemia is influenced by Gene polymorphism of IDH1.