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. 2020 Fall;15(4):299-305.
doi: 10.30699/ijp.2020.121365.2320. Epub 2020 Jul 16.

Thiopurine S-methyltransferase and Pemphigus Vulgaris: A Phenotype-Genotype Study

Maral Mokhtari  1 , Farzaneh Mostanbet  1 , Saideh Nekooee Fard  1 , Golsa Shekarkhar  1 , Mozhdeh Sepaskhah  2 , Maryam Sadat Sadati  2
Affiliations

Thiopurine S-methyltransferase and Pemphigus Vulgaris: A Phenotype-Genotype Study

Maral Mokhtari et al. Iran J Pathol. 2020 Fall.

Abstract

Background & objective: Thiopurine drugs are considered as a treatment modality in various autoimmune disorders including pemphigus vulgaris (PV). These drugs are metabolized by an enzyme "Thiopurine S-methyl transferase" (TPMT). Various variants of this enzyme may have decreased activity leading to serious drug side effects. To investigate the phenotype and genotype of TPMT in PV patients receiving thiopurine drugs.

Methods: A total of 50 patients (29 women and 21 men) with pemphigus vulgaris treating with standard dose of Thiopurine drugs were selected. Sex, age, result of liver function test and complete blood count were recorded. Genotyping of two common non-functional allele (TPMT*2 and TPMT*3C) by Allele-specific and RFLP-PCR was performed. TPMT enzymatic level was determined by an ELISA based method.

Results: Of patients, 36 (72%) were found to have normal TPMT level; and 12, (24%) had higher level of enzyme and 2, 4% had low TPMT enzyme, but none of the patients showed mutant TPMT*2 and TPMT*3C alleles. None of the patients showed hepatotoxicity and bone marrow suppression.

Conclusion: The phenotypic assay based on ELISA method may have false positive and misleading results but genotyping using PCR-RFLP and allele specific PCR is accurate, simple and cost-effective and can be used in patients decided to undergo thiopurine treatment.

Keywords: Allele specific PCR; ELISA test; PCR-RFLP; Thiopurine S- methyl transferase; Thiopurine drugs.

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Figures

Fig. 1
Fig. 1
Allele specific TPMT wild type TPMT*2
Fig. 2
Fig. 2
TPMT Allele specific TPMT*2 mutant type
Fig. 3
Fig. 3
TPMT *3C before adding restriction enzyme (digestion)
Fig. 4
Fig. 4
TPMT*C products after adding digestion enzyme
See this image and copyright information in PMC

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