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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 investigate the polymorphisms of rs4135385, AXIN2 rs11079571, SFRP1 rs7832767 in WNT signaling pathway and the risk of acute leukemia and its treatment The effect of the relationship, provide the basis for individualized treatment. Methods A total of 372 patients with acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL) were treated with 1 ~ 1.5 mL of bone marrow before treatment, and 2.0 mL of venous blood was drawn from 401 healthy controls (control group) The genotypes of CTNNB1 rs4135385, AXIN2 rs11079571 and SFRP1 rs7832767 were genotyped by high resolution melting curve (HRM). The genotypes and allele frequency distributions of three single nucleotide polymorphisms (SNPs) were analyzed by Chi-square test in case group And control group. The differences of clinical characteristics of different genotypes patients were statistically analyzed by one-way ANOVA. The difference of induction rate of complete remission (CR) among different genotypes was analyzed by chi-square test. Results There was no significant difference in genotype and allele frequency distribution between CTNNB1 rs4135385 and SFRP1 rs7832767 loci in AML, ALL patients and controls. Individuals with the A allele at locus AXIN2rs11079571 had a lower risk of developing acute myelomonocytic / monocytic leukemia (AML-M4 / 5) relative to the G allele, with a statistically significant difference (P = 0.016 , OR = 0.677, 95% CI: 0.439-0.930). In addition, patients with AA genotypes had a higher total number of platelets (P = 0.040) and patients with AG and GG genotypes in AML-M4 / 5 patients with the highest CR rate (P = 0.040). Conclusion The frequency of allele A in AXIN2 rs11079571 in AML-M4 / 5 is lower than that in normal controls, and the patients with A allele are associated with higher peripheral platelet count and chemosensitivity.