Department of Hematology, Jiangsu Province Hospital, The First Affiliated Nanjing Medical University Hospital, Nanjing Medical University, 300 Guangzhou Rd, 210029 Nanjing, China.
Med Oncol. 2011 Mar;28(1):265-9. doi: 10.1007/s12032-010-9456-9. Epub 2010 Mar 4.
The human multidrug resistance gene (MDR1, ABCB1) codes for P-glycoprotein (P-gp) that affects the pharmacokinetics of many drugs. MDR1 single nucleotide polymorphisms (SNPs) are associated with drug clearance. Imatinib is a substrate of P-gp-mediated efflux. We investigated the MDR1 T1236C, G 2677T/A, and C3435T polymorphism in 52 patients with chronic myeloid leukemia treated with imatinib. The distribution of MDR1 1236, 2677, or 3435 genotypes was significantly different between the resistance patients and sensitivity patients. The resistance incidence correlated with the number of T alleles at locus 1236 and 3435. Resistance was higher for patients homozygous for the 1236T allele when compared to patients with CT/CC genotype groups (75% vs. 31.3%, P = 0.004). For the G2677T/A polymorphism, a better complete cytogenetic remission was observed for patients with genotype AG/AT/AA, when compared to other genotype groups (TT/GT/GG, P = 0.02). Patients with 3435 TT/CT genotypes showed a higher resistance when compared with patients with CC genotype (59.4% vs. 25%, P = 0.023). In conclusion, determination of 1236T, C3435T, and G2677T MDR1 polymorphisms might be useful in response prediction to therapy with imatinib in patients with CML.
人类多药耐药基因（MDR1，ABCB1）编码 P-糖蛋白（P-gp），影响许多药物的药代动力学。MDR1 单核苷酸多态性（SNPs）与药物清除有关。伊马替尼是 P-糖蛋白介导外排的底物。我们研究了 52 例接受伊马替尼治疗的慢性髓性白血病患者的 MDR1 T1236C、G2677T/A 和 C3435T 多态性。耐药患者和敏感患者的 MDR1 1236、2677 或 3435 基因型分布差异显著。耐药发生率与 1236 位和 3435 位 T 等位基因的数量相关。与 CT/CC 基因型组相比，1236T 等位基因纯合子患者的耐药率更高（75% vs. 31.3%，P = 0.004）。对于 G2677T/A 多态性，与其他基因型组相比，AG/AT/AA 基因型患者的完全细胞遗传学缓解更好（TT/GT/GG，P = 0.02）。与 CC 基因型患者相比，3435 TT/CT 基因型患者的耐药率更高（59.4% vs. 25%，P = 0.023）。总之，MDR1 1236T、C3435T 和 G2677T 多态性的测定可能有助于预测 CML 患者对伊马替尼治疗的反应。
