Abstract
Background: P-glycoprotein (P-gp) is a transmembrane pump encoded by MDR1 gene. It contributes in protection of the cells against xenobiotic and toxic compounds. P-gp also contributes in multidrug resistance in acute lymphoblastic leukemia (ALL). Human MDR1 polymorphism include C to T exchange at position 3435, individuals with TT polymorphism have lower expression of P-gp than the others with CC genotypes. Accumulation of xenobiotics in the cells can cause some diseases like cancers.Materials and Methods: To evaluate MDR1C3435T gene polymorphism in adult patients with ALL, 54 patients and 96 healthy controls were involved in our survey. Genotyping of ALL patients and healthy controls was performed by Polymerase Chain Reaction – Restriction Fragment- Length Polymorphism (PCR-RFLP). Data analysis was done by SPSS software through T-test and Chi- Square. Results: No significant difference was found between C3435T MDR1 gene polymorphisms and incidence of ALL in adult patients. Also there was not any significant difference between T and C alleles and incidence of ALL. Conclusion: C3435T MDR1 polymorphism is not associated with the incidence of ALL in the population studied. Keyword: P-gp; C3435T; MDR1; ALL; polymorphism DOI: 10.3329/jom.v12i1.5541J Medicine 2011; 12 : 3-6
Highlights
Acute lymphoblastic leukemia (ALL) is considered as a clonal lymphoblastic disease that includes about 20% of adult acute leukemias
We showed in our previous study (2010) a predictor role for C3435T multi drug resistance – 1 (MDR1) gene in children with acute lymphoblastic leukemia (ALL), the mutant homozygous TT genotype and heterozygous CT genotype were found to be significantly associated with the occurrence of ALL (p=0.026, odd ratio (OR), 95% CI; 1.96, for TT genotype and p=0.017, OR, 95% CI; 0.53 for TC genotype), (11)
This study showed that C3435T polymorphism of MDR1 gene is not a major predictor for ALL in adults
Summary
Acute lymphoblastic leukemia (ALL) is considered as a clonal lymphoblastic disease that includes about 20% of adult acute leukemias. The difference in P–gp levels between two groups was greater than 65–fold, and affected the pharmacokinetics of the glycoprotein substrate, i.e. digoxin.[9] Previous studies showed a predisposing role for MDR1 C3435T gene polymorphism in children with ALL.[10,11] It is supposed that the lower expression of P-gp can cause accumulation of xenobiotics and toxic compounds in the cell and results in predisposition to diseases such as cancers. P-glycoprotein (P-gp) is a transmembrane pump encoded by MDR1 gene It contributes in protection of the cells against xenobiotic and toxic compounds. Results: No significant difference was found between C3435T MDR1 gene polymorphisms and incidence of ALL in adult patients.
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