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

## TL;DR

This study identifies genetic variations in a Kosovo population that influence how people respond to thiopurine drugs, which could help improve personalized treatment strategies.

## Contribution

The study reports population-specific frequencies of thiopurine-related pharmacogenes in healthy individuals from Kosovo, highlighting unique genetic profiles.

## Key findings

- The MTHFR 677T variant (rs1801133) was significantly more frequent in the Kosovo population (49.8%) compared to global and European averages.
- TPMT*3A and TPMT*3C variant frequencies were 2.0% and 0.1%, respectively, in the studied population.
- NUDT15 rs116855232 was present at a frequency of 0.8%, and PACSIN2 rs2413739 had a minor allele frequency of 48.8%.

## Abstract

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.

Genetic inheritance affects how people respond to medications, which can lead to successful treatments or harmful side effects. This study focuses on thiopurines, drugs used for conditions such as leukemia and organ transplants. Researchers in Kosovo explored genetic differences that influence thiopurine effectiveness and safety. Researchers collected blood samples to analyze genetic variations in five key genes: TPMT, NUDT15, MTHFR, ITPA and PACSIN2. These genes are important because they affect how the body processes thiopurines. The study used techniques such as TaqMan genotyping and Sanger sequencing to identify genetic differences. The results showed that some genetic variations were more common in the Kosovo population compared with global averages. This information is crucial for developing personalized medicine strategies in Kosovo. The researchers concluded that understanding these genetic differences can help tailor treatments to reduce side effects and improve outcomes.

This summary was initially drafted using artificial intelligence, then revised and fact-checked by the author.