Population frequencies of thiopurine-related pharmacogenes in healthy individuals from Kosovo

Pasha, Flaka (author), Urbančič, Dunja (author), Gosheva, Gordana (author), Zhubi, Bukurije (author), Qormemeti, Safete Maliqi (author), Krasniqi, Shaip (author), Mlinarič-Raščan, Irena (author)

Personalized thiopurine therapy is among the most established examples of pharmacogenomics translated into clinical practice. Variants in TPMT (rs1800462, rs1800460, rs1142345) and NUDT15 (rs116855232) are recognized clinical predictors of thiopurine efficacy and toxicity. Additional variants in genes such as PACSIN2 (rs2413739), ITPA (rs1127354) and MTHFR (rs1801133 and rs1801131), also contribute to variability in drug response. Here we characterize the frequency of the pharmacogenetic variants involved in thiopurine metabolism in a healthy population of Kosovo. We genotyped 299 healthy blood donors for polymorphisms. Among TPMT variant alleles, TPMT*3A was observed at a frequency of 2.0%, and the TPMT*3C at 0.1%. Notably, the MTHFR 677T variant (rs1801133) was significantly more frequent in the Kosovo population (49.8%) compared with the global and European frequencies. The minor allele frequency of MTHFR rs1801131 was 27.4%. Minor allele frequencies for PACSIN2 rs2413739 and ITPA rs1127354 variants were 48.8% and 4.0%, respectively. Sequencing of NUDT15 revealed six variants, with rs116855232 present at frequency of 0.8%. These findings provide important insights into the pharmacogenomic profile of the Kosovo population and support the implementation of pre-emptive genotyping to improve the safety and efficacy of thiopurine therapy in the region.

• Language: English
• Keywords: genetics research, pharmacogenomics
• Work type: Article
• Typology: 1.01 - Original Scientific Article
• Organization: FFA - Faculty of Pharmacy
• Publication status: Published
• Publication version: Version of Record
• Year: 2026
• Number of pages: Str. 1-7
• Numbering: Vol. 13, iss. 1, art. 3
• PID: 20.500.12556/RUL-180570
• UDC: 615.015:575.111
• ISSN on article: 2054-345X
• DOI: 10.1038/s41439-026-00337-3
• COBISS.SI-ID: 271195139
• Publication date in RUL: 11.03.2026

Record is a part of a journal

• Title: Human genome variation
• Shortened title: Hum. genome var.
• Publisher: Nature Publishing Group
• ISSN: 2054-345X
• COBISS.SI-ID: 523116057

Licences

• License: CC BY 4.0, Creative Commons Attribution 4.0 International
• Link: http://creativecommons.org/licenses/by/4.0/
• Description: This is the standard Creative Commons license that gives others maximum freedom to do what they want with the work as long as they credit the author.

Secondary language

• Language: Slovenian
• Keywords: genetske preiskave, farmakogenomika