ALOX5基因启动子SP-1结合位点多态性与急性髓系白血病易感性的关系

Relationship between polymorphism of SP-1 binding motif in ALOX5 promoter and susceptibility to acute myeloid leukemia

目的探讨花生四烯5-脂氧合酶基因(arachidonate 5-lipoxygenase gene, ALOX5)基因启动子SP-1结合位点的多态性与成人急性髓系白血病(acute myeloid leukemia, AML)的相关性。方法 采用聚合酶链反应-单链构象多态性(PCR-SSCP)分析236例成人AML(实验组)和179例健康体检者(对照组)中ALOX5基因启动子SP-1结合位点的多态性,经PCR产物直接测序法进行验证,利用DNAStar软件对测序结果进行分析。结果 检测到ALOX5基因启动子SP-1结合位点有6种基因型,包括4/4、4/5、4/6、5/5、5/6和6/6。在实验组和对照组中,基因型4/4的分布频率为20.30%和10.10%( OR =1.976,95% CI :1.050~3.719,χ 2=4.539, P <0.05);基因型4/6的分布频率为10.60%和26.80%( OR =0.386,95% CI :0.215~0.692,χ 2=10.513, P <0.05);等位基因6的分布频率为26.90%和30.20%( OR =0.736,95% CI :0.528~1.025,χ 2=3.291, P <0.05);SP-1位点的其余基因型、等位基因在实验组和对照组中分布频率差异无统计学意义( P >0.05),其可能不是成人AML发病风险的预警指标。结论 ALOX5基因启动子区SP-1结合位点的基因型4/6,等位基因6可能与AML发病风险降低有关,而携带基因型4/4人群可能易患AML。

Purpose To analyses the association between polymorphism of SP-1 binding motif in ALOX5 promoter and the susceptibility to adult acute myeloid leukemia (AML). Methods 236 patients with AML and 179 healthy people as the control group are enrolled in the research. Polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP) was applied to test the polymorphism of SP-1 binding motif in ALOX5. The genotype was further determined by directly sequence PCR amplification products. The sequences data of the genotype were edited by using DNAStar software. Results Six genotypes of SP-1 binding motif in ALOX5 were detected by PCR-SSCP, including 4/4, 4/5, 4/6, 5/5, 5/6 and 6/6 genotypes. In the experiment group and the control group, the distributions of 4/4 genotype ratio was 20.30% and 10.10%( OR =1.976, 95% CI : 1.050~3.719,χ 2=4.539, P <0.05), the 4/6 genotype ratio was 10.60% and 26.80%( OR =0.386, 95% CI : 0.215~0.692,χ 2=10.513, P <0.05), and the distribution of the allele ratio of 6 was 26.90% and 38.50%( OR =2.06, 95% CI : 1.486~2.855,χ 2=19.039, P <0.01). There were no significant difference in the other genotype and allele distribution of SP-1 polymorphism between the experimental group and the control group ( P >0.05), which may not be associated to the susceptibility to AML. Conclusion The genotype 4/6 and allele 6 of SP-1 binding motif in ALOX5 promoter may be linked to the susceptibility confers a reduced risk of AML, whereas the genotype 4/4 may shows the susceptibility to adult AML.