Single nucleotide polymorphisms of multidrug resistance gene 1 (MDR1) and risk of chronic myeloid leukemia
Multidrug resistance gene 1 (MDR1) is known for its involvement in the detoxification through the active transport of toxic compounds from diverse origins outside the cells. These compounds could cause injury to cell DNA, which might lead in cancer like chronic myeloid leukemia (CML). Individual inherited genetic differences related to polymorphism in detoxification enzymes could be an important factor not only in carcinogen metabolism but also in susceptibility of cancer. The present study aimed to investigate the association of three single nucleotide polymorphisms (SNPs) of the MDR1 gene in the susceptibility of CML. We successively have determined the genotype profiles of 1236C>T (exon 12); 2677G>T (exon 21), and 3435C>T (exon 26) SNPs by PCR-RFLP in 89 patients and 99 unrelated healthy controls. Logistic regression was used to assess the effect of each SNP on the development of CML. Interestingly, in exon 12, the 1236TT was significantly associated with the susceptibility of CML when compared to the wild type 1236CC (OR 2.7; 95 % CI 1–7.32, p = 0.041). Additionally, the recessive model 1236TT vs. 1236CC/CT showed a risk of 3.3 fold (p = 0.011) with CML. In exon 26, the 3435CT genotype was associated with a reduced risk of CML (OR 0.5; 95 % CI 0.3–1, p = 0.042). In exon 21, the 2677GT genotype seems to have a protective effect (OR 0.6; 95 % CI 0.32–1.1, p = 0.074). Diplolotypes analysis has demonstrated no effect in susceptibility of CML, but 1236CT/3435CC and 1236CC/2677GT were associated with a protective effect. The haplotypes analysis showed no particular trend (global association p = 0.33). Our findings demonstrate that 1236TT in exon 12 might contribute in the susceptibility of CML, while the 3435CT in exon 26 as well as 1236CT/3435CC and 1236CC/2677GT combinations might be protective factors.
KeywordsMDR1 gene Polymorphism CML
We authors thank the Hassan II Academy of Science and Technology by supporting this study financially.
Conflicts of interest
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