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Vitamin K Epoxide Reductase Complex (VKORC1) Electrochemical Genosensors: Towards the Identification of 1639 G>A Genetic Polymorphism

2025-07-10Research article Open access
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dc.contributor.authorBarbosa, Tiago
dc.contributor.authorMorais, Stephanie L.
dc.contributor.authorCarvalho, Renato
dc.contributor.authorMagalhães, Júlia M. C. S.
dc.contributor.authorDomingues, Valentina F.
dc.contributor.authorDelerue-Matos, Cristina
dc.contributor.authorFerreira-Fernandes, Hygor
dc.contributor.authorPinto, Giovanny R.
dc.contributor.authorSantos, Marlene
dc.contributor.authorBarroso, Maria Fátima
dc.contributor.authorSantos, Marlene
dc.contributor.authorManuel de Caldevilla Carvalho, Renato
dc.date.accessioned2025-07-10T14:20:22Z
dc.date.available2025-07-10T14:20:22Z
dc.date.issued2025-07-10
dc.description.abstractAnticoagulants, including warfarin, are often administered to patients who are exhibiting early symptoms of thromboembolic episodes or who have already experienced such episodes. However, warfarin has a limited therapeutic index and might cause bleeding and other clinical problems. Warfarin inhibits the vitamin K epoxide reductase complex subunit 1 (VKORC1), an enzyme essential for activating vitamin K, in the coagulation cascade. Genetic factors, such as polymorphisms, can change the natural function of VKORC1, causing variations in the medication reaction among individuals. Hence, before prescribing warfarin, the patient’s genetic profile should also be considered. In this study, an electrochemical genosensor capable of detecting the VKORC1 1639 G>A polymorphism was designed and optimized. This analytical approach detects the electric current obtained during the hybridization reaction between two 52 base pair complementary oligonucleotide sequences. Investigating public bioinformatic platforms, two DNA sequences with the A and G single-nucleotide variants were selected and designed. The experimental protocol of the genosensor implied the formation of a bilayer composed of a thiolate DNA and an alkanethiol immobilized onto gold electrodes, as well as the formation of a DNA duplex using a sandwich-format hybridization reaction through a fluorescein labelled DNA signalling probe and the enzymatic amplification of the electrochemical signal, detected by chronoamperometry. A detection limit of 20 pM and a linear range of 0.05–1.00 nM was obtained. A clear differentiation between A/A, G/A and G/G genotypes in biological samples was successfully identified by his novel device.por
dc.description.sponsorshipGENOPSYSEN-ref:223RT0141 COMPETE2030-FEDER-00699000
dc.identifier.citationBarbosa, T., Morais, S. L., Carvalho, R., Magalhães, J. M. C. S., Domingues, V. F., Delerue-Matos, C., Ferreira-Fernandes, H., Pinto, G. R., Santos, M., & Barroso, M. F. (2025). Vitamin K Epoxide Reductase Complex (VKORC1) Electrochemical Genosensors: Towards the Identification of 1639 G>A Genetic Polymorphism. Chemosensors, 13(7), Artigo 7. https://doi.org/10.3390/chemosensors13070248
dc.identifier.doi10.3390/chemosensors13070248
dc.identifier.issn2227-9040
dc.identifier.urihttp://hdl.handle.net/10400.22/30220
dc.language.isoeng
dc.peerreviewedyes
dc.publisherMDPI
dc.relationUID/50006
dc.relation.hasversionhttps://www.mdpi.com/2227-9040/13/7/248
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/
dc.subjectCardiovascular diseases
dc.subjectElectrochemical genosensors
dc.subjectSingle-nucleotide polymorphisms
dc.subjectVKORC1
dc.subjectWarfarin
dc.titleVitamin K Epoxide Reductase Complex (VKORC1) Electrochemical Genosensors: Towards the Identification of 1639 G>A Genetic Polymorphismpor
dc.typeresearch article
dspace.entity.typePublication
oaire.citation.issue7
oaire.citation.titleChemosensors
oaire.citation.volume13
oaire.versionhttp://purl.org/coar/version/c_970fb48d4fbd8a85
person.familyNameSantos
person.familyNameManuel de Caldevilla Carvalho
person.givenNameMarlene
person.givenNameRenato
person.identifier1508370
person.identifier2868531
person.identifier.ciencia-id8311-B967-31C4
person.identifier.ciencia-id4817-5B7F-4D35
person.identifier.orcid0000-0001-5020-5942
person.identifier.orcid0009-0009-5272-4178
person.identifier.scopus-author-id57110502000
relation.isAuthorOfPublication8ce9ee39-a4c6-46ae-99e2-49397b550f1b
relation.isAuthorOfPublicationfa11c04f-84f8-4db3-8a2d-8e9fe13fe991
relation.isAuthorOfPublication.latestForDiscovery8ce9ee39-a4c6-46ae-99e2-49397b550f1b

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