Publication
Development of an electrochemical DNA-based biosensor for the detection of the cardiovascular pharmacogenetic-altering SNP CYP2C9*3
| dc.contributor.author | Morais, Stephanie L. | |
| dc.contributor.author | Magalhães, Júlia M.C. S. | |
| dc.contributor.author | Domingues, Valentina F. | |
| dc.contributor.author | Delerue-Matos, Cristina | |
| dc.contributor.author | Ramos-Jesus, Joilson | |
| dc.contributor.author | Ferreira-Fernandes, Hygor | |
| dc.contributor.author | Pinto, Giovanny R. | |
| dc.contributor.author | Santos, Marlene | |
| dc.contributor.author | Barroso, M. Fátima | |
| dc.date.accessioned | 2023-09-11T15:34:17Z | |
| dc.date.available | 2023-09-11T15:34:17Z | |
| dc.date.issued | 2023-06-01 | |
| dc.description.abstract | Cardiovascular diseases are among the major causes of mortality and morbidity. Warfarin is often prescribed for these disorders, an anticoagulant with inter and intra-dosage variability dose required to achieve the target international normalized ratio. Warfarin presents a narrow therapeutic index, and due to its variability, it can often be associated with the risk of hemorrhage, or in other patients, thromboembolism. Single-nucleotide polymorphisms are included in the causes that contribute to this variability. The Cytochrome P450 (CYP) 2C9*3 genetic polymorphism modifies its enzymatic activity, and hence warfarin's plasmatic concentration. Thus, the need for a selective, rapid, low-cost, and real-time detection device is crucial before prescribing warfarin. In this work, a disposable electrochemical DNA-based biosensor capable of detecting CYP2C9*3 polymorphism was developed. By analyzing genomic databases, two specific 78 base pairs DNA probes; one with the wild-type adenine (Target-A) and another with the cytosine (Target-C) single-nucleotide genetic variation were designed. The biosensor implied the immobilization on screen-printed gold electrodes of a self-assembled monolayer composed by mercaptohexanol and a linear CYP2C9*3 DNA-capture probe. To improve the selectivity and avoid secondary structures a sandwich format of the CYP2C9*3 allele was designed using complementary fluorescein isothiocyanate-labeled signaling DNA probe and enzymatic amplification of the electrochemical signal. Chronoamperometric measurements were performed at a range of 0.015–1.00 nM for both DNA targets achieving limit of detection of 42 p.m. The developed DNA-based biosensor was able to discriminate between the two synthetic target DNA targets, as well as the targeted denatured genomic DNA, extracted from volunteers genotyped as non-variant homozygous (A/A) and heterozygous (A/C) of the CYP2C9*3 polymorphism. | pt_PT |
| dc.description.version | info:eu-repo/semantics/publishedVersion | pt_PT |
| dc.identifier.citation | Morais, S. L., Magalhães, J. M. C. S., Domingues, V. F., Delerue-Matos, C., Ramos-Jesus, J., Ferreira-Fernandes, H., Pinto, G. R., Santos, M., & Barroso, M. F. (2023). Development of an electrochemical DNA-based biosensor for the detection of the cardiovascular pharmacogenetic-altering SNP CYP2C9*3. Talanta, 264, 124692. https://doi.org/10.1016/j.talanta.2023.124692 | pt_PT |
| dc.identifier.doi | 10.1016/j.talanta.2023.124692 | pt_PT |
| dc.identifier.eissn | 1873-3573 | |
| dc.identifier.issn | 0039-9140 | |
| dc.identifier.uri | http://hdl.handle.net/10400.22/23504 | |
| dc.language.iso | eng | pt_PT |
| dc.peerreviewed | yes | pt_PT |
| dc.publisher | Elsevier | pt_PT |
| dc.relation.publisherversion | https://www.sciencedirect.com/science/article/pii/S0039914023004435?via%3Dihub | pt_PT |
| dc.subject | Cardiovascular diseases | pt_PT |
| dc.subject | Chronoamperometry | pt_PT |
| dc.subject | Electrochemical DNA-Based biosensor | pt_PT |
| dc.subject | Sandwich format hybridization | pt_PT |
| dc.subject | Single-nucleotide polymorphism | pt_PT |
| dc.title | Development of an electrochemical DNA-based biosensor for the detection of the cardiovascular pharmacogenetic-altering SNP CYP2C9*3 | pt_PT |
| dc.type | journal article | |
| dspace.entity.type | Publication | |
| oaire.citation.endPage | 10 | pt_PT |
| oaire.citation.startPage | 1 | pt_PT |
| oaire.citation.title | Talanta | pt_PT |
| oaire.citation.volume | 264 | pt_PT |
| person.familyName | Santos | |
| person.givenName | Marlene | |
| person.identifier | 1508370 | |
| person.identifier.ciencia-id | 8311-B967-31C4 | |
| person.identifier.orcid | 0000-0001-5020-5942 | |
| person.identifier.scopus-author-id | 57110502000 | |
| rcaap.rights | closedAccess | pt_PT |
| rcaap.type | article | pt_PT |
| relation.isAuthorOfPublication | 8ce9ee39-a4c6-46ae-99e2-49397b550f1b | |
| relation.isAuthorOfPublication.latestForDiscovery | 8ce9ee39-a4c6-46ae-99e2-49397b550f1b |