Genetic profiling of NUDT15 in the Slovenian population

Šmid, Alenka (avtor), Urbančič, Dunja (avtor), Vrevc Žlajpah, Jaka (avtor), Stollarova, Natalia (avtor), Prelog, Tomaž (avtor), Kavčič, Marko (avtor), Jazbec, Janez (avtor), Mlinarič-Raščan, Irena (avtor), Karas Kuželički, Nataša (avtor)

Determining variant TPMT alleles to predict patient response to thiopurine therapy represents one of the first successful implementations of pharmacogenomics in clinical practice. However, despite the TPMT-adjusted thiopurine dosing, some TPMT wild-type patients still exhibit toxicity at standard doses. Over the past decade, the pharmacogene NUDT15 has emerged as a significant co-modulator of thiopurine therapy. Initially, NUDT15 was considered important predominantly in Asian populations, but recent studies have highlighted its relevance in European populations as well. To evaluate the pharmacogenetic significance of NUDT15 in the Slovenian population, we sequenced extended regions of exon 1 and exon 3 in 109 healthy individuals and 37 patients with acute lymphoblastic leukemia. We identified eight variants, including one with established clinical significance (allele *3) and one extremely rare variant (Chr13 at 48045861; GRCh38, NC_000013.11). The frequencies of most previously described variants in both the general population and in the ALL cohort were consistent with those reported in other European populations, except for rs45465203, which was less frequent in the Slovenian population. None of the variants, except for NUDT15*3, were associated with cumulative thiopurine doses in ALL patients. However, these variants warrant further investigation in larger ALL cohorts.

• Jezik: Angleški jezik
• Ključne besede: 6-mercaptopurine, acutelymphoblastic leukemia, dose reduction, minorallele frequency, NUDT15, population genetics, thiopurines
• Vrsta gradiva: Članek v reviji
• Tipologija: 1.01 - Izvirni znanstveni članek
• Organizacija: FFA - Fakulteta za farmacijo ; MF - Medicinska fakulteta
• Različica publikacije: Objavljena publikacija
• Leto izida: 2024
• Št. strani: Str. 515-525
• Številčenje: Vol. 25, no. 12-13
• PID: 20.500.12556/RUL-165844
• UDK: 616.155.392+575.17
• ISSN pri članku: 1744-8042
• DOI: 10.1080/14622416.2024.2409060
• COBISS.SI-ID: 213081347
• Datum objave v RUL: 12.12.2024

Gradivo je del revije

• Naslov: Pharmacogenomics
• Skrajšan naslov: Pharmacogenomics
• Založnik: Future Medicine
• ISSN: 1744-8042
• COBISS.SI-ID: 521752601

Licence

• Licenca: CC BY-NC-ND 4.0, Creative Commons Priznanje avtorstva-Nekomercialno-Brez predelav 4.0 Mednarodna
• Povezava: http://creativecommons.org/licenses/by-nc-nd/4.0/deed.sl
• Opis: Najbolj omejujoča licenca Creative Commons. Uporabniki lahko prenesejo in delijo delo v nekomercialne namene in ga ne smejo uporabiti za nobene druge namene.

Sekundarni jezik

• Jezik: Slovenski jezik
• Ključne besede: 6-merkaptopurin, NUDT15, zmanjšanje odmerka, pogostnost manjšega alela, tiopurini, akutna limfoblastna levkemija, populacijska genetika