12个候选单核苷酸多态性位点与中国儿童急性淋巴细胞白血病易感性和预后的关系

目的：探讨12 个候选单核苷酸多态性（SNP）位点和中国儿童急性淋巴细胞白血病（ALL）易感性及预后的关系。方法：复习文献选取12 个候选SNP位点，采用多重PCR后靶向捕获二代测序技术检测各SNP的基因型。采用χ2检验及logistic回归分析对556 例ALL患儿和191 例健康志愿者进行病例-对照研究验证SNP位点与中国儿童ALL易感性的关系。采用Kaplan-Meier生存分析及Cox回归分析365 例ALL患儿SNP位点与ALL预后的关系。结果：Logistic回归分析显示SNP位点基因型与ALL风险增加显著相关：ARID5B 基因的rs10821936 风险等位基因C（OR =1.687，95%CI =1.318～2.135，P ＜0.001］和rs10994982 风险等位基因A（OR =1.594，95%CI =1.259～2.018，P ＜0.001），IKZF1 基因的rs11978267 风险等位基因G（OR =2.133，95%CI =1.495～3.043，P ＜0.001）和rs4132601风险等位基因G（OR =2.108，95%CI =1.466～3.031，P ＜0.001）以及ZNF230 基因的rs7554607 风险等位基因C（OR =1.481，95%CI =1.161～1.890，P =0.002）。多因素Cox回归分析显示无事件生存率的不良预后因素：SIAT7C 基因的rs10873876 位点TC基因型（HR =2.111，95%CI =1.260～3.539，P =0.005）以及LOC102723724 基因的rs11155133 位点GG基因型（HR =4.787，95%CI =1.652～13.870，P =0.004），同时它们也是复发率的不良预后因素（前者HR =2.082，95%CI =1.242～3.492，P =0.005，后者HR =4.067，95%CI =1.380～11.988，P =0.011）。结论：ARID5B 基因的rs10821936和rs10994982、ZNF230基因的rs7554607以及IKZF1 基因的rs11978267 和rs4132601为我国儿童ALL潜在易感性位点。SIAT7C 基因的rs10873876以及LOC102723724 基因的rs11155133多态性位点可作为ALL患儿的预后因素。

The relationship of 12 candidate single nucleotide polymorphisms with susceptibility and prognosis of acute lymphoblastic leukemia in Chinese children

Objective: To investigate the relationship of 12 candidate single nucleotide polymorphisms(SNP) loci with the susceptibility and prognosis of Chinese children with acute lymphoblastic leukemia (ALL).Methods: Review the literature and select 12 candidate SNP loci, and then detect the genotype of each SNP by multiplex PCR targeted capture next-generation sequencing technology. A case-control study on 556 children with ALL and 191 healthy volunteers was conducted using chi-square test and logistic regression analysis to verify the relationship between SNP loci and the susceptibility of Chinese children with ALL. Kaplan-Meier survival analysis and Cox regression were used to analyze the relationship between SNP loci and the prognosis of ALL in 365 ALL cases. Results: Logistic regression analysis showed that the genotype of the SNP locus was significantly correlated with the increased risk of ALL: the rs10821936 risk allele C (OR=1.687, 95%CI=1.318-2.135, P<0.001) and rs10994982 risk allele A (OR=1.594, 95%CI=1.259-2.018, P<0.001) of the ARID5B gene;rs11978267 risk allele G (OR=2.133, 95%CI=1.495-3.043, P<0.001) and rs4132601 risk allele G (OR=2.108,95%CI=1.466-3.031, P<0.001) of the IKZF1 gene and the rs7554607 risk allele C (OR=1.481, 95%CI=1.161-1.890, P=0.002) of the ZNF230 gene. Multivariate Cox regression analysis showed that the following were an poor prognostic factor of event-free survival rate: TC genotype at rs10873876 locus of SIAT7C gene (HR=2.111,95%CI=1.260-3.539, P=0.005) and GG genotype at rs11155133 locus of LOC102723724 gene (HR=4.787,95%CI=1.652-13.870, P=0.004). At the same time, they were also poor prognostic factors of recurrence rate (the former HR=2.082, 95%CI=1.242-3.492, P=0.005, the latter HR=4.067, 95%CI=1.380-11.988, P=0.011).Conclusion: The rs10821936 and rs10994982 of ARID5B gene, rs7554607 of ZNF230 gene, rs11978267 and rs4132601 of IKZF1 gene are the potential susceptibility loci of ALL in Chinese children. Polymorphism loci of rs10873876 of SIAT7C and rs11155133 of LOC102723724 can be prognostic factors for childhood ALL.