【摘要】 目的研究我国汉族人群基因多态性与成人急性白血病易感性的关系。方法按照1:1配对病例对照方法采集江苏汉族人群成人急性白血病病例与对照的外周血,应用PCR-RFLP技术,从代谢酶、受体、DNA修复基因三个层面检测CYP1A1(C6235T)、GSTT1、GSTM1、NQO1(C609T)、P2X7(A1513C)、XRCC1(Arg399Gln)、XPD(Lys751Gln)基因多态性的分布,分析上述基因位点多态性和成人急性白血病易感性的关系。以及基因与基因间的交互作用。结果应用配对病例对照的x2检验分析得出CYP1A1、P2X7、XPD突变型和GSTT1缺失基因型在病例与对照组中的分布有统计学差异(P<0.05),CYP1A1、GSTT1、P2X7、XPD基因可能是成人急性白血病的易感基因,其OR值分别为3.1957、1.9008、1.9983和2.1842;按病理类型分析,CYP1A1可能是急性髓性白血病、CYP1A1与XPD可能是急性淋巴细胞性白血病的易感基因。应用logistic多元回归模型分析得出CYP1A1(6235T)与XRCC1(399Gin)突变基因型之间,P2X7(1513C)与XRCC1(399Gln)突变基因型之间具有协同作用,其OR值分别为5.720和5.027,有统计学意义(P<0.05)。结论携带CYP1A1、P2X7、XPD突变等位基因者.携带GSTT1缺失型基因者患急性白血病的危险性可能增加;其中携带CYP1A1突变等位基因者患成人急性髓性白血病的危险性可能增加,携带CYP1A1与XPD突变等位基因者患成人急性淋巴细胞性白血病的危险性可能增加;同时携带CYP1A1(6235T)与XRCC1(399Gln)突变基因型或P2X7(1513C)与XRCC1(399Gln)突变基因型患成人急性白血病的危险性比单独携带其中一个突变基因型者明显增加。更多还原

【Abstract】 Objective To explore the possible relationship between genetic polymorphisms and susceptibility for adult acute leukemia in Chinese Han population. Methods The genetic polymorphisms of 4 metabolic enzymest CYP1A1C6235T, GSTT1, GSTM1, NQO1C609T, receptor P2X7 A1513C, and 2 DNA repair genes:XRCC1 Arg399Gln and XPDLys751Gln were genotyped by PCR-RFLP analysis in peripheral blood DNA samples of 1 : 1 for paired cases and controls. Results The CYP1A1, GSTT1, P2X7 ,XPD were susceptible genes of adult acute leukemia with OR of 3. 1957,1. 9008,1. 9983 and 2. 1842, respectively(P< 0. 05). The CYP1A1 was susceptible gene for AML. The CYP1A1 and XPD were susceptible genes for ALL. Both the interactions between CYP1A16235 and XRCC1399 mutant genotypes, and between P2X71513 and XRCC1399 were found to have syner-gistic effect to the occurrence of acute leukemia with OR of 5. 720 and 5. 027(P<0. 05) , respectively. Conclusion Individuals with the CYP1A16235T, GSTT1null, P2X7 1513c, XPD751Gln mutant genotypes might significantly enhance the risk of acute leukemia; individuals with the CYP1A16235T mutant genotype might relate to AML; and the CYP1A16235T or XPD751Gln might relate to ALL. Individuals both with CYP1A16235T and XRCC1 399Gln mutant genotypes or P2X7 1513 and XRCC1399 mutant genotypes presented significantly higher risks for the acute leukemia than with only one of the two mutant genotypes.更多还原