药物代谢酶基因多态性与初治急性髓系白血病初次诱导治疗结果的相关性研究

Relationships Between the Gene Polymorphisms of Drug Metabolizing Enzymes and the Outcome of the First Induction Chemotherapy in Patients with de novo Acute Myeloid Leukemia

本研究目的是研究药物代谢酶基因多态性与初治急性髓系白血病(AML)初次诱导治疗结果的相关性,以113名初治急性髓系白血病患者为研究对象,采用SNP分型系统对药物代谢酶的11个单核苷酸多态性位点进行基因分型。应用逻辑回归比较各基因型分布情况与患者初次诱导治疗缓解率的关系。结果表明,多因素分析结果显示CYP2D6(rs16947)多态性位点的非野生型患者缓解率明显低于野生型患者,差异具有统计学意义(p=0.033,OR=0.32,95%CI 0.112-0.915);GSTO2(rs156697)多态性位点非野生型缓解率明显高于野生型患者,差异具有统计学意义(p=0.011,OR=3.023,95%CI 1.289-7.089);将两基因多态性位点进行联合分析,结果显示CYP2D6为非野生型基因且GSTO2野生型基因型(V+W)患者的缓解率明显低于两基因均为野生型(W+W)患者,差异具有统计学意义(p=0.017,OR=0.183,95%CI 0.045-0.735)。结论:CYP2D6(rs16947)和GSTO2(rs156697)基因多态性是影响初治急性髓系白血病初次诱导化疗缓解的独立因素。

The objective of this study was to investigate the correlation between the gene polymorphisms of drug metabolizing enzymes and the outcome of the first induction chemotherapy in patients with de novo acute myeloid leukemia（AML）.113 de novo AML patients were enrolled in this study.The genotypes of 11 single nucleotide polymorphisms（SNP） in drug metabolizing enzymes were detected by the SNPstream Genotyping System.The correlation between the distribution of genotypes and the complete remission rate of first induction chemotherapy was analyzed by logical regression.The results showed that patients with variant genotype of CYP2D6（rs16947） had a lower conplete remission（CR） rate,as compared to those with wild type（p=0.033,OR=0.32,95% CI 0.112-0.915）;meanwhile the patients with variant genotype of GSTO2（rs156697）had a higher CR rate as compared to those with wild type（p=0.011,OR=3.023,95% CI 1.289-7.089）.Combined analysis of the above polymorphisms,showed that patients with variant genotype of CYP2D6 and wild genotype of GSTO2（V＋W） had lower CR rates in comparison to patients with wild genotypes of both polymorphisms（p=0.017,OR=0.183,95% CI 0.045-0.735）.It is concluded that CYP2D6（rs16947） and GSTO2（rs156697） polymorphisms are independent factors influencing CR rates of the first induction chemotherapy in de novo AML patients.