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dc.contributorVall d'Hebron Barcelona Hospital Campus
dc.contributor.authorFarinango, Camila
dc.contributor.authorGallardo-Cóndor, Jennifer
dc.contributor.authorFreire Paspuel, Byron
dc.contributor.authorFlores-Espinoza, Rodrigo
dc.contributor.authorJaramillo-Koupermann, Gabriela
dc.contributor.authorLópez-Cortés, Andrés
dc.date.accessioned2022-09-12T09:35:15Z
dc.date.available2022-09-12T09:35:15Z
dc.date.issued2022-06-10
dc.identifier.citationFarinango C, Gallardo-Cóndor J, Freire-Paspuel B, Flores-Espinoza R, Jaramillo-Koupermann G, López-Cortés A, et al. Genetic Variations of the DPYD Gene and Its Relationship with Ancestry Proportions in Different Ecuadorian Trihybrid Populations. J Pers Med. 2022 Jun 10;12(6):950.
dc.identifier.issn2075-4426
dc.identifier.urihttp://hdl.handle.net/11351/8149
dc.descriptionEcuadorian ethnic groups; Fluoropyrimidines; Pharmacogenetics
dc.description.abstractDihydropyrimidine dehydrogenase is one of the main pharmacological metabolizers of fluoropyrimidines, a group of drugs widely used in clinical oncology. Around 20 to 30% of patients treated with fluoropyrimidines experience severe toxicity caused by a partial or total decrease in enzymatic activity. This decrease is due to molecular variants in the DPYD gene. Their prevalence and allelic frequencies vary considerably worldwide, so their description in heterogeneous groups such as the Ecuadorian population will allow for the description of pharmacogenetic variants and proper characterization of this population. Thus, we genotyped all the molecular variants with a predictive value for DPYD in a total of 410 Ecuadorian individuals belonging to Mestizo, Afro-Ecuadorian, and Indigenous ethnic groups. Moreover, we developed a genetic ancestry analysis using 46 autosomal ancestry informative markers. We determined 20 genetic variations in 5 amplified regions, including 3 novel single nucleotide variants. The allele frequencies for DPYD variants c.1627G>A (*5, rs1801159), c.1129-15T>C (rs56293913), c.1218G>A (rs61622928), rs1337752, rs141050810, rs2786783, rs2811178, and g.97450142G>A (chr1, GRCh38.p13) are significantly related to Native American and African ancestry proportions. In addition, the FST calculated from these variants demonstrates the closeness between Indigenous and Mestizo populations, and evidences genetic divergence between Afro-Ecuadorian groups when compared with Mestizo and Indigenous ethnic groups. In conclusion, the genetic variability in the DPYD gene is related to the genetic component of ancestral populations in different Ecuadorian ethnic groups. The absence and low frequency of variants with predictive value for fluoropyrimidine toxicity such as DPYD *2A, HapB3, and c.2846A>T (prevalent in populations with European ancestry) is consistent with the genetic background found.
dc.language.isoeng
dc.publisherMDPI
dc.relation.ispartofseriesJournal of Personalized Medicine;12(6)
dc.rightsAttribution 4.0 International
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/
dc.sourceScientia
dc.subjectCàncer - Tractament
dc.subjectAntimetabòlits - Efectes secundaris
dc.subjectGenètica
dc.subject.meshAntimetabolites, Antineoplastic
dc.subject.mesh/adverse effects
dc.subject.meshGenetic Variation
dc.subject.meshNeoplasms
dc.titleGenetic Variations of the DPYD Gene and Its Relationship with Ancestry Proportions in Different Ecuadorian Trihybrid Populations
dc.typeinfo:eu-repo/semantics/article
dc.identifier.doi10.3390/jpm12060950
dc.subject.decsantimetabolitos antineoplásicos
dc.subject.decs/efectos adversos
dc.subject.decsvariación genética
dc.subject.decsneoplasias
dc.relation.publishversionhttps://doi.org/10.3390/jpm12060950
dc.type.versioninfo:eu-repo/semantics/publishedVersion
dc.audienceProfessionals
dc.contributor.organismesInstitut Català de la Salut
dc.contributor.authoraffiliation[Farinango C, Gallardo-Cóndor J] Facultad de Ingeniería y Ciencias Aplicadas, Universidad de Las Américas, Quito, Ecuador. [Freire-Paspuel B] Laboratorios de Investigación, Universidad de Las Américas, Quito, Ecuador. Vall d’Hebron Institut de Recerca (VHIR), Barcelona, Spain. Vall d’Hebron Hospital Universitari, Barcelona, Spain. [Flores-Espinoza R] Laboratorios de Investigación, Universidad de Las Américas, Quito, Ecuador. Laboratório de Diagnóstico por DNA (LDD), Universidade do Estado do Rio de Janeiro, Rio de Janeiro, Brazil. [Jaramillo-Koupermann G] Laboratorio de Biología Molecular, Subproceso de Anatomía Patológica, Hospital de Especialidades Eugenio Espejo, Quito, Ecuador. [López-Cortés A] Escuela de Medicina, Facultad de Ciencias de la Salud, Universidad de Las Américas, Quito, Ecuador. Programa de Investigación en Salud Global, Facultad de Ciencias de la Salud, Universidad Internacional SEK, Quito, Ecuador. Latin American Network for the Implementation and Validation of Clinical Pharmacogenomics Guidelines (RELIVAF-CYTED), Madrid, Spain
dc.identifier.pmid35743735
dc.identifier.wos000816343500001
dc.rights.accessrightsinfo:eu-repo/semantics/openAccess


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