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目的研究多药耐药基因(MDR1)12外显子 C1236T、21外显子 G2677T/A、26外显子C3435T 基因多态性与急性髓细胞白血病(AML)化疗预后相关性。方法本研究纳入44位 AML 患者,采用聚合酶链反应-限制性片段长度多态性(PCR-RFLP)方法以及直接测序的方法分析了患者MDR1第12、21、26位点基因型,并在诱导化疗第一疗程结束后进行骨髓形态学检查,结合临床指标判断患者是否完全缓解。x~2分析 MDR1各等位基因的分布是否符合 Hardy-Weinberg 平衡,完全缓解(CR)率与临床特征的相关性使用 x~2分析或 Fisher’s精确检验。结果中国人 C1236T、G2677T/A 和C3435T 基因突变发生频率与其他种族相比差异有统计学意义,中国健康人以上三个位点基因型发生频率与急性髓细胞白血病患者相比差异无统计学意义。初发 AML 患者外周血白细胞数量与 CR 率有显著相关性(x~2=7.207,P=0.007);MDR1 C1236T 及 C3435T 基因多态性与 CR 率无显著相关性(P=0.349,P=0.074);MDR1 G2677T/A 多态性与 CR 率有显著相关性(x~2=6.214,P=0.045),携带G/G 基因型患者与非 G/G 基因型患者相比 CR 率较低(x~2=6.142,P=0.013);携带 MDR1 C3435TC/T 基因型患者与携带非 C/T 基因型患者相比 CR 率较低(x~2=3.991,P=0.046),同时显著低于 T/T基因型患者(x~2=5.134,P=0.023)。结论 MDR1外显子12、21、26基因型发生频率存在种族差异,AML 患者以上三个位点基因型发生频率与健康人相比差异无统计学意义。G2677T/A 基因多态性可以作为预测 AML 患者第一疗程是否 CR 的预测因素,为个体化给药提供理论基础。
Objective To investigate the association between polymorphism of exon C2636T, exon C2635T and exon C3435T in patients with acute myeloid leukemia (AML) and multidrug resistance gene (MDR1) 12 exon C1236T. Methods A total of 44 patients with AML were enrolled in this study. Genotypes at 12, 21 and 26 of MDR1 were analyzed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and direct sequencing. Induction chemotherapy after the first course of bone marrow morphology, combined with clinical indicators to determine whether the patient was completely relieved. The distributions of MDR1 alleles were in accordance with Hardy-Weinberg equilibrium. The correlation between CR rates and clinical features was analyzed using x2 analysis or Fisher’s exact test. Results The frequencies of C1236T, G2677T / A and C3435T mutations in Chinese were significantly different from those in other races. There was no significant difference in genotype frequency between the above three loci in Chinese healthy people and patients with acute myeloid leukemia . There was a significant correlation between the number of peripheral leukocytes and the CR rate in newly diagnosed AML patients (x ~ 2 = 7.207, P = 0.007). There was no significant correlation between the polymorphisms of MDR1 C1236T and C3435T and the CR rate (P = 0.349, ). There was a significant correlation between MDR1 G2677T / A polymorphism and CR rate (x ~ 2 = 6.214, P = 0.045). CR rate was lower in patients with G / G genotype than those with non G / G genotype patients with MDR1 C3435TC / T genotype had lower CR rate (x ~ 2 = 3.991, P = 0.046) than those with non-C / T genotype T / T genotype patients (x ~ 2 = 5.134, P = 0.023). Conclusion There are racial differences in the frequency of genotypes of exon 12, 21, and 26 in MDR1. There was no significant difference in the frequency of genotypes among the above three loci in patients with AML compared with healthy controls. G2677T / A gene polymorphism can be used as a predictor of CR in the first course of AML patients, providing a theoretical basis for individualized administration.