WNT信号通路相关基因多态性与急性白血病遗传易感性的相关性研究

Genetic Polymorphisms in Wnt Signaling Pathway and Acute Leukemia

目的探讨WNT信号通路中β-链蛋白基因（CTNNB1）rs4135385位点、轴蛋白基因（AXIN2）rs11079571位点及分泌型卷曲相关蛋白基因（SFRP1）rs7832767位点多态性与急性白血病发病风险和治疗效果的关系,为个体化治疗提供依据。方法对372例急性髓细胞白血病（AML）及急性淋巴细胞白血病（ALL）患者在治疗前抽取骨髓液1~1.5 mL,401例健康对照（对照组）抽取静脉血2.0 mL,提取总DNA,用高分辨熔解曲线（HRM）方法进行CTNNB1rs4135385、AXIN2rs11079571、SFRP1rs7832767基因分型,并通过卡方检验分析3个单核苷酸多态性（SNP）位点的基因型和等位基因频率分布在病例组和对照组中的差异,用单因素方差检验统计不同基因型患者的临床特征的差异,用卡方检验分析不同基因型患者诱导化疗完全缓解（CR）率的差异。结果CTNNB1rs4135385、SFRP1rs7832767位点的基因型及等位基因频率分布在AML、ALL患者组与对照组中的差异均无统计学意义。AXIN2rs11079571位点携带A等位基因的个体相对于G等位基因个体,发生急性粒单核/单核细胞白血病（AML-M4/5）的发病风险较低,差异有统计学意义（P=0.016,OR=0.677,95%CI：0.439~0.930）。此外,在AML-M4/5患者中,AA基因型患者相对于AG和GG基因型患者有较高的血小板总数（P=0.040）,且诱导化疗CR率最高（P=0.040）。结论在AML-M4/5中AXIN2rs11079571位点的A等位基因频率低于正常对照组,并且携带A等位基因患者伴有较高外周血小板总数和诱导化疗敏感性。

Objective To determine the impacts of Wnt signaling pathway products-polymorphisms of rs4135385,rs11079571 and rs7832767located inβ-catenin gene（CTNNB1）,Axin gene（AXIN2）,and secreted frizzled-related protein gene（SFRP1）on the risk and treatment outcomes of acute leukemia.Methods Bone marrows（volume 1-1.5 mL）were collected from 372 untreated patients with acute myeloid leukemia（AML）or acute lymphoblastic leukemia（ALL）,and peripheral blood samples（2.0 mL）were obtained from 401 healthy controls for the purpose of total DNA extraction.Polymorphisms of rs4135385,rs11079571 and rs7832767located in CTNNB1,AXIN2 and SFRP1 were genotyped with high-resolution melting method（HRM）.Chi-square analyses were performed to compare the genotype and allele distributions of the three single nucleotides（SNPs）between the leukemia patients and healthy controls.Single factor variance tests were performed to compare the differences in clinical features among different genotype groups.Complete remission（CR）rates after induction chemotherapy were also compared between different genotype groups using Chi-square tests.Results No significant differences were found between the leukemia patients and healthy controls in the frequencies of alleles and genotypes of CTNNB1rs4135385,SFRP1rs7832767 polymorphisms.Those with A allele in AXIN2rs11079571 polymorphism was less likely to have acute myelomonocytic/monocytic leukemia than those with G allele（P=0.016,OR=0.677,95%CI：0.439-0.930）.Acute bead monocyte/mononuclear cell leukemia（AML-M4/5）patients with AA genotype presented higher platelet count（P =0.040）,and higher complete remission rate after chemotherapy（P=0.040）,compared with the patients with AG and GG genotypes.Conclusion AML-M4/5patients have less frequency of A allele in AXIN2rs11079571 polymorphism than healthy controls.Patients carrying A allele have higher platelet counts and higher sensitivity to chemotherapy.