Genetic Polymorphism of the Thiopurine S-Methyltransferase Gene: A Tertiary Care Setup Study

Noman Ur Rehman; Zujaja Hina Haroon; Ahsan Hussain; Hoor Gulalai Kakakhem

doi:10.51253/pafmj.v75i3.10557

Authors

Noman Ur Rehman Department of Chemical Pathology, Armed Forces Institute of Pathology /National University of Medical Sciences (NUMS), Rawalpindi Pakistan
Zujaja Hina Haroon Department of Chemical Pathology, Armed Forces Institute of Pathology /National University of Medical Sciences (NUMS), Rawalpindi Pakistan
Ahsan Hussain Department of Chemical Pathology, Armed Forces Institute of Pathology /National University of Medical Sciences (NUMS), Rawalpindi Pakistan
Hoor Gulalai Kakakhem Department of Chemical Pathology, Armed Forces Institute of Pathology /National University of Medical Sciences (NUMS), Rawalpindi Pakistan

DOI:

https://doi.org/10.51253/pafmj.v75i3.10557

Keywords:

Inflammatory Bowel Disease, Real-Time PCR, Thiopurine Drugs, TPMT Gene, TPMT Variant Alleles, Wild Type Alleles.

Abstract

Objective: To determine Thiopurine s-Methyl Transferase (TPMT) gene variants in patients reporting to a Tertiary Care Hospital in Pakistan.

Study Design: Cross-sectional study.

Place and Duration of Study: Armed Forces Institute of Pathology, Rawalpindi Pakistan, from May 2022 to Jun 2023.

Methodology: A total of 110 patients diagnosed with Inflammatory Bowel Disease and using were included in this study. DNA was extracted following the GeneJet genomic DNA purification method. Genotype for the respective mutation of extracted DNA for Thiopurine s-Methyl Transferase (TPMT) genes was determined using real-time Polymerase Chain Reaction (PCR) with the use of fluorescently labelled probes specifically on the principle of allelic discrimination. Gene and allele frequencies were calculated. Expected genotype frequencies were calculated using Hardy-Weinberg equation. Gene and allele frequencies were compared with expected frequencies using Chi square test to reveal any deviation from Hardy-Weinberg equilibrium.

Results: Among 110 patients enrolled in the study, 102 patients (92.7%) were found to have wild type alleles. Eight patients (7.3%) had variant (mutated) alleles of TPMT. Among these patients, 7(6.4%) had heterozygous allelic pattern, 5 had TPMT*3C while 2 had TPMT*3B. One patient (0.9%) was found homozygous TPMT*3C variant alleles. TPMT*2 variant was not found in any of the patient. Frequencies did not reveal any deviation from Hardy-Weinberg equilibrium (p>0.05).

Conclusion: TPMT*3C was the most common genetic variant found in heterozygous pattern. Gene and allele frequencies showed no deviation from the Hardy-Weinberg equilibrium.

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