Thiopurine S-Methyltransferase Polymorphism in Iraqi Paediatric Patients with Acute Lymphoblastic Leukaemia
Published: January 1, 2019 | DOI: https://doi.org/10.7860/JCDR/2019/38404.12501
Nawars Mohammed, Manalk Rasheed, Hasanein H Ghali
1. College of Medicine, Department of Clinical Biochemistry, University of Baghdad, Baghdad, Iraq.
2. College of Medicine, Department of Clinical Biochemistry, University of Baghdad, Baghdad, Iraq.
3. College of Medicine, Department of Paediatrics, University of Baghdad, Baghdad, Iraq.
Correspondence
Dr. Nawars Mohammed,
College of Medicine, Department of Clinical Biochemistry, University of Baghdad, Iraq.
E-mail: nawarsmm@yahoo.com
Introduction: Acute Lymphoblastic Leukaemia (ALL) treatment protocols widely used thiopurine drugs as an anti-cancer agent, which over the course of time results in drug toxicity. Thiopurine S-Methyltransferase Enzyme (TPMT) is responsible for the activation of 6-Mercaptopurine (6-MP) to Thioguanine Nucleotides (TGNs) that are incorporated into DNA and trigger cell death. Low TPMT activity is strongly correlated to TPMT genetic polymorphism.
Aim: To identify the level of TPMT activity and the most common TPMT polymorphism (TPMT*3A, TPMT*3B and TPMT*3C) and its frequencies in a sample of Iraqi ALL paediatric patients.
Materials and Methods: Eighty-one Iraqi ALL paediatric patients receiving 6-MP in the maintenance phase of treatment were enrolled in the study. TPMT activity in the serum was measured by using Enzyme-Linked Immunosorbent Assay Technique (ELISA) in the serum and TPMT genetic polymorphism (TPMT*3A, TPMT*3B and TPMT*3C) was detected by allele-specific multiplex-PCR analysis. Statistical analysis was performed by using a two-sample t-test to evaluate the difference in allele frequencies proportion in TPMT polymorphism. Pearson’s correlation analysis was done to determine the correlation between TPMT enzyme genotype and phenotype.
Results: There were 51 paediatric ALL patients carrying the wild-type allele with allele frequencies of (62.96%), 30 paediatric ALL patients carrying the mutant alleles either TPMT*3A or TPMT*3C with allele frequencies of 29.62% and 7.4% respectively. The mutant allele TPMT*3B was not detected in the patients under study. The difference in mean of the TPMT enzyme activity between the ALL patients carrying the wild-type allele and the mutant allele was highly significant with p-value =0.001. A highly significant positive co-relation (r=0.939) was found between TPMT low activity and presence of genetic mutation across the TPMT gene (p-value=0.001).
Conclusion: TMPT genotyping and phenotyping is an essential tool to reduce the cytotoxic effects of the anti-cancer drug 6-MP in Iraqi paediatric patients with ALL for a successful recovery.
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