Association of TPMT (rs1800460) Gene Polymorphism with Childhood Acute Lymphoblastic Leukemia in a Population from Guilan, Iran

Document Type: Research Article


1 Department of Cell and Molecular Biology, University of Guilan, Rasht, Iran

2 Department of Biology, Faculty of Sciences, University of Guilan, Rasht, Iran

3 Guilan University of Medical Sciences, Rasht, Iran

4 Department of Biology, Rasht Branch, Islamic Azad University, Rasht, Iran



Acute lymphoblastic leukemia (ALL) is a malignant transformation and proliferation of lymphoid progenitor cells in bone marrow and blood, which is mainly found in children. Thiopurine methyltransferase (TPMT) is a thiopurine drug metabolizer enzyme that is prescribed for the treatment of ALL. Several single nucleotide polymorphisms in the TPMT gene have been reported to be associated with the decreased and deficient activity of the enzyme, which disrupts thiopurine drug metabolization and results in severe hematopoietic toxicity, which could be fatal in the patients. Since genetic screening before the thiopurine drug treatment of patients could be helpful for dosage optimization and efficient chemotherapy, this study was conducted to evaluate the association of G>A 146 TPMT gene polymorphism (rs1800460) with ALL susceptibility in an Iranian childhood population from the province of Guilan. This case-control study was performed on 400 individuals including 200 patients and 200 healthy children. Allele-specific PCR (AS-PCR) was applied to genotype the polymorphism of the TPMT gene. We found a significant difference in genotype distributions of G>A 146 TPMT polymorphism between patients and controls (p = 0.0001). Our results showed that individuals with the GA genotype had significantly increased risk of ALL (OR = 3.66, %95CI = 1.87-7.17, p = 0.0001), whereas individuals with the AA genotype were not associated with the increased risk of ALL (p = 0.2). This study may provide useful information for early diagnosis and an optimized strategy for the treatment of patients. However, more studies must perform for further characterization of this issue.


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