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NUDT15, MRP4 and the development of precision medicine in Chile


Pharmacy & Pharmacology International Journal
Alonso De la Rivera Morales,1,2 Dominique Yañez Osorio,2 Carolina Salas Palma,2 Caroline Weinstein Oppenhimer3

Abstract

The genetic structure in Chile is heterogeneous and identifying native, African, European, and Asian components. Increasing the uncertainty about the frequency of genotypic variants and diversifying the response to chemotherapeutic drugs in our population. The individualization of the dose based on Pharmacogenomics is essential to achieve the expected effects of the treatment being more effective and avoiding the toxic effects of drugs such as 6-Mercaptopurine, the main pharmacological agent in acute lymphoblastic leukemia. Whose metabolization is affected by single nucleotide polymorphisms (SNPs) in the enzyme NUDT15 (rs116855232) and the protein MRP4 (rs3765534) related to drug resistance. Both of which cause leukopenia and myelosuppression in patients at standard doses and are not available for detection in Chile. The background of the prevalence of 8.8% in Uruguay and 12.5% in Mexico of the SNP in NUDT15. In addition to international clinical guidelines that recommend reducing the dose by up to 80% depending on the genotype. Is of interest for the development of new techniques in laboratories. In this project both SNPs were implemented using real-time PCR and validated by sequencing being the basis for future studies related to frequencies and their relationship with adverse events. Providing key antecedents for antineoplastic treatment and contributing to the development of a medicine of accuracy in the country.

Keywords

NUDT15, MRP4, pharmacogenomics, 6-Mercaptopurine, precision medicine

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