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Warfarin pharmacogenomics: Designing electrochemical DNA-based sensors to detect CYP2C9*2 gene variation

2025-03-24Research article Open access
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dc.contributor.authorBarbosa, Tiago
dc.contributor.authorMorais, Stephanie L.
dc.contributor.authorPereira, Eduarda
dc.contributor.authorMagalhães, Júlia M. C. S.
dc.contributor.authorDomingues, Valentina F.
dc.contributor.authorFerreira-Fernandes, Hygor
dc.contributor.authorPinto, Giovanny
dc.contributor.authorSantos, Marlene
dc.contributor.authorBarroso, Maria Fátima
dc.contributor.authorSantos, Marlene
dc.date.accessioned2025-03-25T15:33:31Z
dc.date.available2025-03-25T15:33:31Z
dc.date.issued2025-03-24
dc.description.abstractThe CYP2C9 enzyme is involved in the metabolism of warfarin. The CYP2C9 gene harbors several single-nucleotide polymorphisms (SNPs), including CYP2C9*2 (rs1799853), which is known to affect warfarin’s therapeutic response. So, it is important to develop analytical tools capable of genotyping these SNPs to adjust warfarin’s therapeutic outcomes. In this work, an electrochemical DNA-based sensor was constructed and optimized for the detection of the CYP2C9*2 polymorphism. Methods: Using bioinformatic database platforms, two 71 base pair DNA target probes with the polymorphic variants A and G were chosen and designed. A DNA-based sensor was composed by mercaptohexanol and the CYP2C9*2 DNA capture probe in a self-assembled monolayer connected to screen-printed gold electrodes. Two independent hybridization events of the CYP2C9*2 allele were designed using complementary fluorescein-labeled DNA signaling to improve selectivity and avoid secondary structures. Three human samples with the homozygous variant (G/G) and non-variant (A/A) and heterozygous (G/A) genotypes were amplified by PCR and then applied to the developed genosensor. Results: Chronoamperometry measurements were performed for both polymorphic probes. A calibration curve in the 0.25 to 2.50 nM (LOD of 13 pM) and another in the 0.15 to 5.00 nM range (LOD of 22.6 pM) were obtained for the homozygous non-variant and variant probes, respectively. This innovative tool was capable of identifying the hybridization reaction between two complementary strands of immobilized DNA, representing a genotyping alternative to the classical PCR methodology. Conclusions: The developed electrochemical DNA-based sensor was able to discriminate two synthetic SNP target sequences (Target-A and Target-G) and detect, with specificity, the three patients’ genotypes (G/G, G/A, and A/A). This tool is therefore a promising, sensitive, and cost-effective analytical way to determine and discriminate an individual’s genotype and predict the appropriate warfarin dose.por
dc.identifier.citationBarbosa, T., Morais, S. L., Pereira, E., Magalhães, J. M. C. S., Domingues, V. F., Ferreira-Fernandes, H., Pinto, G., Santos, M., & Barroso, M. F. (2025). Warfarin Pharmacogenomics: Designing Electrochemical DNA-Based Sensors to Detect CYP2C9*2 Gene Variation. Genes, 16(4), Artigo 4. https://doi.org/10.3390/genes16040372
dc.identifier.doi10.3390/genes16040372
dc.identifier.urihttp://hdl.handle.net/10400.22/29860
dc.language.isoeng
dc.peerreviewedyes
dc.publisherMDPI
dc.relationUID/50006; 2020.03107.CEECIND-DOI:10.54499/2020.03107.CEECIND/CP1596/CT0005
dc.relation.hasversionhttps://www.mdpi.com/2073-4425/16/4/372
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/
dc.subjectCardiovascular diseases
dc.subjectCYP2C9*2
dc.subjectElectrochemical DNA-based sensor
dc.subjectPersonalized medicine
dc.subjectPharmacogenetics
dc.subjectSingle-nucleotide polymorphisms
dc.titleWarfarin pharmacogenomics: Designing electrochemical DNA-based sensors to detect CYP2C9*2 gene variationpor
dc.typeresearch article
dspace.entity.typePublication
oaire.citation.endPage14
oaire.citation.issue4
oaire.citation.startPage1
oaire.citation.titleGENES
oaire.citation.volume16
oaire.versionhttp://purl.org/coar/version/c_970fb48d4fbd8a85
person.familyNameSantos
person.givenNameMarlene
person.identifier1508370
person.identifier.ciencia-id8311-B967-31C4
person.identifier.orcid0000-0001-5020-5942
person.identifier.scopus-author-id57110502000
relation.isAuthorOfPublication8ce9ee39-a4c6-46ae-99e2-49397b550f1b
relation.isAuthorOfPublication.latestForDiscovery8ce9ee39-a4c6-46ae-99e2-49397b550f1b

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