Polymorphisms and haplotypes in multidrug resistance 1 (MDR1) gene and their association with clinical outcome of some Iraqi patients with acute leukemia.

Abstract

The human multidrug resistance (MDR1, ABCB1) gene encodes P-glycoprotein (P-gp), which affects the pharmacokinetics of many drugs. Polymorphisms in ABCB1 might contribute to cancer risk and therapeutic response. Here, we investigated whether common MDR1 single nucleotide polymorphisms (SNPs) (C1236T, C3435T, and G2677T/A) and their expressed levels associated with clinical outcome of acute leukemia. Genotyping was performed in 46 patients with acute leukemia (AL) by direct sequencing analysis resulting in a total of 31 AML and 15 ALL cases matched with 10 samples healthy control. There was a high significant difference in the heterozygous haplotype B (CTGTCT) of MDR1 associated with high level of MDR1 mRNA expression (p=0.0017**: 3.21 ± 0.24) in non-responder (NR) patients with AML patients. While a mutant homozygous C (TTT) haplotype was found to be associated in both NR and CR ALL patients (p=0.0428* and 0.0336*) respectively, with high level of MDR1 gene expression (1.14 ± 0.05 and 1.25 ± 0.03). We conclude that B haplotype of MDR1 associated with poor prognosis of AML, while the C mutant haplotype of MDR1 was associated with ALL but there was no significant differences with clinical outcomes.