Single nucleotide polymorphisms of multidrug resistance gene 1 (MDR1) and risk of chronic myeloid leukemia

Abstract

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 1236 C>T (exon 12); 2677 G>T (exon 21), and 3435 C>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 1236 TT was significantly associated with the susceptibility of CML when compared to the wild type 1236 CC (OR 2.7; 95% CI 1-7.32, p = 0.041). Additionally, the recessive model 1236 TT vs. 1236 CC/CT showed a risk of 3.3 fold (p = 0.011) with CML. In exon 26, the 3435 CT genotype was associated with a reduced risk of CML (OR 0.5; 95% CI 0.3-1, p = 0.042). In exon 21, the 2677 GT 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 1236 CT/3435 CC and 1236 CC/2677 GT were associated with a protective effect. The haplotypes analysis showed no particular trend (global association p = 0.33). Our findings demonstrate that 1236 TT in exon 12 might contribute in the susceptibility of CML, while the 3435 CT in exon 26 as well as 1236 CT/3435 CC and 1236 CC/2677 GT combinations might be protective factors.

The single nucleotide polymorphism and haplotype analysis of MDR1 in Chinese diffuse large B cell lymphoma patients

“…while the heterozygous 3435CT in Exon 26 seemed to have a 169 protective effect [19]. These significant findings were not found in 170 our study.…”

“…2677GT genotype seemed to have a protective effect in CML 164 (OR = 0.6; 95% CI: 0.32-1.1, P = 0.074) [19]. Genetic background 165 and the tumor originations may play an important role for the 166 different associations.…”

“…136 Diplotype of 1236CT/2677GTwas also more common in DLBCL 137 group than the controls (24.03% in DLBCL group vs. 13 hematologic diseases is worthy to be further investigated 150 [10,19]. We have reported the MDR1 correlations in chronic 151 lymphocytic leukemia (CLL) and chronic myeloid leukemia (CML) 152 in our patients, and some relevant prognostic factors as well as 153 drug resistance were also explored [5,20].…”

MDR1 polymorphisms have an impact on the prognosis of Chinese diffuse large B cell lymphoma patients

“…P-gp is encoded by the human multidrug resistance-1 gene (MDR1), located on chromosomal region 7q21.1 [6]. Some single nucleotide polymorphism (SNP) studies in MDR1 gene have indicated their effect on gene expression and/or protein function, which might be associated with development of cancers, chemotherapy response, and clinical prognosis in tumor patients [8][9][10]. Among the discovered SNPs, C1236T (Exon 12, rs1128503), C3435T (Exon 26, rs1045642), and G2677T/A (Exon 21, rs2032582) are the most common and mainly focused on polymorphisms in the coding region of MDR1 [11][12][13].…”

Genetic Polymorphisms of Multidrug Resistance Gene‐1 (MDR1/ABCB1) and Glutathione S‐Transferase Gene and the Risk of Inflammatory Bowel Disease among Moroccan Patients

“…Genotyping of C1236T and C3435T SNPs was done by polymerase chain reaction, restrictive fragment length polymorphism. The primer sequences, enzymatic restriction conditions, and digestion product sizes were previously described [ 26 , 27 ]. To identify the genotypes of GSTM1 and GSTT1 , a multiplex polymerase chain reaction (PCR) was performed, in which BCL2 gene was used as an internal control.…”