20.500.12556/DiRROS-30162 Genetic profiling of NUDT15 in the Slovenian population 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. 6-mercaptopurine acutelymphoblastic leukemia dose reduction minorallele frequency NUDT15 population genetics thiopurines 6-merkaptopurin NUDT15 zmanjšanje odmerka pogostnost manjšega alela tiopurini true false true Angleški jezik Slovenski jezik Neznano 2026-06-16 11:58:41 2026-06-16 11:58:41 2026-06-17 03:46:51 0000-00-00 00:00:00 2024 0 0 Nasl. z nasl. zaslona; Opis vira z dne 28. 10. 2024; str. 515-525 no. 12-13 Vol. 25 2024 0000-00-00 Zaloznikova Objavljeno NiDoloceno 0000-00-00 0000-00-00 0000-00-00 616.155.392+575.17 1744-8042 10.1080/14622416.2024.2409060 213081347 RAZ_Smid_Alenka_2024.pdf RAZ_Smid_Alenka_2024.pdf 1 11549AB1D1AD562223943245F9BDFD25 01b5f6dd57b1c1f9f1dbf20eebfc89a81dc0e51e722301899e9f16fe38517a55 2acf05b4-696a-11f1-97b2-001a4af901a5 https://dirros.openscience.si/Dokument.php?lang=slv&id=45635 https://www.tandfonline.com/doi/full/10.1080/14622416.2024.2409060 1 f6178620-6969-11f1-97b2-001a4af901a5 https://dirros.openscience.si/Dokument.php?lang=slv&id=45634 Univerzitetni klinični center Ljubljana 0 0 0