Polymorphisms evaluation of the thiopurine s-methyltransferase gene among the iranian acute lymphoblastic leukemia population

Soha Sadeghi,1,* Arvin haghighatfard,2 Tayebetalebzadeh,3 Ali dezhgir,4

1. Department of Cellular and Molecular Biology, Nour Danesh Institute Of Higher Education.
2. Department of biology, Tehran north branch, Islamic Azad University
3. Department of Microbiology, Varamin-Pishva Branch, Islamic Azad University
4. Department of biology, Tehran north branch, Islamic Azad University



thiopurine s-methyltransferase (tpmt) is a cytosolic enzyme which catalyzing the s-methylation of 6-mercaptopurine and azathioprine. thiopurine drugs are widely used for the treatment of acute leukemia, inflammatory bowel diseases, and other immunological disorders. patients with low tmpt activity could develop severe myelosuppression when they are treated with standard doses of thiopurine drugs. present study aimed to evaluate the tpmt gene in iranian acute lymphoblastic leukemia (all) patients.


It was surveyed tpmt gene polymorphism in 50 children with all and 100 healthy subjects. real time polymerase chain reaction polymorphism (real time pcr) and primer-specific pcr-based assays were used to assess the tpmt gene for the variants *2 c.238 g›c, *3a (c.460 g›a, c.719 a›g), *3b (c.460 g›a), and *3c (c.719 a›g).


Results were showed that tpmt variants were significantly associated with low enzymatic activity that was detected in 20.25% of adult iranian individuals and children with all. the frequency of total mutant alleles was 18.83%. no tpmt*3c, tpmt*3b and tpmt*3a allelic variants and no homozygous or compound heterozygous mutant alleles were detected.


Findings have been showed high frequency of tpmt*2 among children with all versus healthy blood donors, and could be used for find the doses of thiopurine drugs based on genotype of tpmt variants in patients.


thiopurine s-methyltransferase ,acute lymphoblastic leukemia (all), polymorphism, tpmt*2