Introducing a fast and simple PCR-RFLP analysis for the detection of mutant thiopurine S-methyltransferase alleles TPMT*3A and TPMT*3C

Journal of the European Academy of Dermatology and Venereology : JEADV
K OenderJ W Bauer

Abstract

Azathioprine, in combination with corticosteroids, is the first-line therapy of severe forms of pemphigus vulgaris. Patients with an impaired thiopurine S-methyltransferase (TPMT) activity are at risk of developing severe myelo-suppression upon treatment with thiopurines such as azathioprine. Analysis of the TPMT status prior to drug administration is therefore highly recommended. However, because of the limited availability of TPMT testing outside of specialized centres, pre-emptive TPMT testing is not widespread. To avoid laborious biochemical and sequencing assays, we evaluated a new restriction fragment length polymorphism (RFLP) analysis. We designed a rapid genetic polymerase chain reaction (PCR)-RFLP screen for the most prevalent mutant TPMT*3A and TPMT*3C alleles that are known to result in reduced TPMT enzyme activity. Validating our fast system on 871 Caucasian DNA samples, we observed that 8.61% of our probands carried the TPMT*3A allele and 0.23% were heterozygous for the TPMT*3C allele, which is in concordance with previously reported allele frequencies. This simple and low-cost PCR-RFLP TPMT polymorphism testing approach can be performed in a standard laboratory. It should be applied to all patients prior to recei...Continue Reading

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Citations

Sep 20, 2011·Dermatologic Clinics·Martin LaimerHelmut Hintner
Aug 4, 2015·International Journal of Dermatology·Mariola Rychlik-SychElżbieta Waszczykowska
Jul 16, 2010·European Journal of Clinical Investigation·Olivier DewitXavier Roblin
Nov 20, 2018·Endocrine, Metabolic & Immune Disorders Drug Targets·Paria PashazadehMasoud Khoshnia

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