The Examination of a TPMT Gene Before Administration of Azathioprine in Rheumatology Practice and Identification of a Novel Variant p.W29R

Abstract

Background: In individuals with reduced thiopurine S-methyltransferase activity, undesirable adverse effects can occur during treatment with azathioprine (AZA). This condition affects approximately 11% of the European population, and it is genetically determined by variants in the TPMT gene. Approximately 0.3% of those of European origin have dysfunctional TPMT variants, which puts them at risk of developing life-threatening bone marrow toxicity. Our goal was to estimate the prevalence of TPMT gene mutations in Czech patients with rheumatic diseases and to assess the adverse effects associated with AZA therapy in these patients.Methods: Two-hundred patients were assessed for the presence of genetic allelic variants using PCR amplification and direct sequencing. Results:In 19 patients, we detected genetic allelic variants affecting TPMT activity; in 1 case, it was an unpublished heterozygous variant c.85T>C (p.W29R); of those, 15 patients were switched from AZA to a different medication, and 1 patient was prescribed a reduced dose of AZA.Conclusions: Our findings show the importance of testing for variants of the TPMT gene before the administration of AZA in clinical rheumatology practice. Patients with documented episodes of leukopenia or elevated liver biochemical tests while on AZA should undergo TPMT genotype testing and/or TPMT enzyme activity testing.