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

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00023728%3A_____%2F22%3AN0000070" target="_blank" >RIV/00023728:_____/22:N0000070 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/00064165:_____/22:10442760 RIV/00216208:11110/22:10442760

Výsledek na webu

<a href="https://pubmed.ncbi.nlm.nih.gov/34870401/" target="_blank" >https://pubmed.ncbi.nlm.nih.gov/34870401/</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1097/RHU.0000000000001727" target="_blank" >10.1097/RHU.0000000000001727</a>

Jazyk výsledku

angličtina

Název v původním jazyce

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

Popis výsledku v původním jazyce

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 Results In 19 patients, we detected genetic allelic variants affecting TPMT activity; in 1 case, it was an unpublished heterozygous variant c.85T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.

Název v anglickém jazyce

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

Popis výsledku anglicky

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.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

30226 - Rheumatology

Projekt

—

Návaznosti

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2022

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

Journal of clinical rheumatology : practical reports on rheumatic & musculoskeletal diseases

ISSN

1076-1608

e-ISSN

1536-7355

Svazek periodika

28

Číslo periodika v rámci svazku

2

Stát vydavatele periodika

US - Spojené státy americké

Počet stran výsledku

7

Strana od-do

E363-E367

Kód UT WoS článku

000759079900018

EID výsledku v databázi Scopus

2-s2.0-85125010632