The Distribution of TPMT Gene Variants in the Population of the Republic of Srpska: Implications for Personalized Thiopurine Therapy
Ključne reči:
TPMT gene, allelic variants, thiopurine, pharmacogenetics, genotyping, Republic of Srpska, personalized therapyApstrakt
Introduction: Thiopurine drugs are widely administered for autoimmune and inflammatory diseases, as well as malignancies. The enzyme thiopurine S-methyltransferase, encoded by the TPMT gene, plays a crucial role in drug metabolism. Knowledge of the frequency and distribution of TPMT allelic variants facilitates personalized treatment and prevention of adverse effects.
Aim: To investigate the frequency and distribution of the most prevalent TPMT allelic variants (*2, *3A, *3C) among the Caucasoid population in the Republic of Srpska. This distribution will help estimate risk for drug-related toxicity and allow tailored thiopurine use.
Materials and Methods: A total of 100 unrelated healthy volunteers from various regions of the Republic of Srpska were included. Genotyping for *2, *3A, and *3C allelic variants was performed using real-time PCR.
Results: Minor allele frequency for *2 was 0.23% (95% CI: 0,04–1,32%); *3B and *3C both had a frequency of 2.83% (95% CI: 1,63–4,88%). 5,66% of subjects were CT or TC genotype carriers for *3B and *3C, respectively. One (0.47%) carried the CG genotype for *2. Co-occurrence of heterozygous *3B and *3C genotypes indicated a *3A haplotype frequency of 2.83%. Among 12 carriers of the *3A genotype, 4 were female and 8 male, with no significant sex differences (p > 0.05). All genotype frequencies were in Hardy-Weinberg equilibrium.
Conclusion: Most subjects are likely to safely metabolize thiopurines at standard doses, but identifying intermediate metabolizers by genetic testing is necessary to prevent serious adverse reactions.
