Identificación y asociación de polimorfismos de Toll-Like Receptor 3 con el desarrollo de Leishmaniasis mucosa frente a la coinfección Leishmania spp. – Leishmania RNA Virus 1

ilustraciones, gráficas, tablas

Autores:: Vargas León, Carolina María

Tipo de recurso:

Fecha de publicación:: 2021

Institución:: Universidad Nacional de Colombia

Repositorio:: Universidad Nacional de Colombia

Idioma:: spa

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network_acronym_str	UNACIONAL2
network_name_str	Universidad Nacional de Colombia
repository_id_str
dc.title.spa.fl_str_mv	Identificación y asociación de polimorfismos de Toll-Like Receptor 3 con el desarrollo de Leishmaniasis mucosa frente a la coinfección Leishmania spp. – Leishmania RNA Virus 1
dc.title.translated.eng.fl_str_mv	Identification and association of Toll-Like Receptor 3 polymorphisms with the development of mucosal Leishmaniasis against the coinfection Leishmania spp. - Leishmania RNA Virus 1
title	Identificación y asociación de polimorfismos de Toll-Like Receptor 3 con el desarrollo de Leishmaniasis mucosa frente a la coinfección Leishmania spp. – Leishmania RNA Virus 1
spellingShingle	Identificación y asociación de polimorfismos de Toll-Like Receptor 3 con el desarrollo de Leishmaniasis mucosa frente a la coinfección Leishmania spp. – Leishmania RNA Virus 1 610 - Medicina y salud::616 - Enfermedades Leishmaniasis Receptor 3 Toll-Like Leishmania Leishmaniasis Toll-Like Receptor 3 Leishmania Leishmania LRV1 TLR3 Leishmaniasis mucosa Leishmaniasis cutánea Polimorfismo de nucleótido único Colombia rs3775296 rs764010322 rs3775291 rs3775290 Mucosal leishmaniasis Cutaneous leishmaniasis Single nucleotide polymorphism
title_short	Identificación y asociación de polimorfismos de Toll-Like Receptor 3 con el desarrollo de Leishmaniasis mucosa frente a la coinfección Leishmania spp. – Leishmania RNA Virus 1
title_full	Identificación y asociación de polimorfismos de Toll-Like Receptor 3 con el desarrollo de Leishmaniasis mucosa frente a la coinfección Leishmania spp. – Leishmania RNA Virus 1
title_fullStr	Identificación y asociación de polimorfismos de Toll-Like Receptor 3 con el desarrollo de Leishmaniasis mucosa frente a la coinfección Leishmania spp. – Leishmania RNA Virus 1
title_full_unstemmed	Identificación y asociación de polimorfismos de Toll-Like Receptor 3 con el desarrollo de Leishmaniasis mucosa frente a la coinfección Leishmania spp. – Leishmania RNA Virus 1
title_sort	Identificación y asociación de polimorfismos de Toll-Like Receptor 3 con el desarrollo de Leishmaniasis mucosa frente a la coinfección Leishmania spp. – Leishmania RNA Virus 1
dc.creator.fl_str_mv	Vargas León, Carolina María
dc.contributor.advisor.spa.fl_str_mv	Echeverry Gaitán, María Clara Cadavid Gutiérrez, Luis Fernando
dc.contributor.author.spa.fl_str_mv	Vargas León, Carolina María
dc.contributor.researchgroup.spa.fl_str_mv	Infecciones y Salud en El Trópico
dc.subject.ddc.spa.fl_str_mv	610 - Medicina y salud::616 - Enfermedades
topic	610 - Medicina y salud::616 - Enfermedades Leishmaniasis Receptor 3 Toll-Like Leishmania Leishmaniasis Toll-Like Receptor 3 Leishmania Leishmania LRV1 TLR3 Leishmaniasis mucosa Leishmaniasis cutánea Polimorfismo de nucleótido único Colombia rs3775296 rs764010322 rs3775291 rs3775290 Mucosal leishmaniasis Cutaneous leishmaniasis Single nucleotide polymorphism
dc.subject.decs.spa.fl_str_mv	Leishmaniasis Receptor 3 Toll-Like Leishmania
dc.subject.decs.eng.fl_str_mv	Leishmaniasis Toll-Like Receptor 3 Leishmania
dc.subject.proposal.spa.fl_str_mv	Leishmania LRV1 TLR3 Leishmaniasis mucosa Leishmaniasis cutánea Polimorfismo de nucleótido único Colombia
dc.subject.proposal.none.fl_str_mv	rs3775296 rs764010322 rs3775291 rs3775290
dc.subject.proposal.eng.fl_str_mv	Mucosal leishmaniasis Cutaneous leishmaniasis Single nucleotide polymorphism
description	ilustraciones, gráficas, tablas
publishDate	2021
dc.date.issued.none.fl_str_mv	2021
dc.date.accessioned.none.fl_str_mv	2022-01-11T21:18:30Z
dc.date.available.none.fl_str_mv	2022-01-11T21:18:30Z
dc.type.spa.fl_str_mv	Trabajo de grado - Maestría
dc.type.driver.spa.fl_str_mv	info:eu-repo/semantics/masterThesis
dc.type.version.spa.fl_str_mv	info:eu-repo/semantics/acceptedVersion
dc.type.content.spa.fl_str_mv	Text
dc.type.redcol.spa.fl_str_mv	http://purl.org/redcol/resource_type/TM
status_str	acceptedVersion
dc.identifier.uri.none.fl_str_mv	https://repositorio.unal.edu.co/handle/unal/80802
dc.identifier.instname.spa.fl_str_mv	Universidad Nacional de Colombia
dc.identifier.reponame.spa.fl_str_mv	Repositorio Institucional Universidad Nacional de Colombia
dc.identifier.repourl.spa.fl_str_mv	https://repositorio.unal.edu.co/
url	https://repositorio.unal.edu.co/handle/unal/80802 https://repositorio.unal.edu.co/
identifier_str_mv	Universidad Nacional de Colombia Repositorio Institucional Universidad Nacional de Colombia
dc.language.iso.spa.fl_str_mv	spa
language	spa
dc.relation.indexed.spa.fl_str_mv	Bireme
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dc.publisher.spa.fl_str_mv	Universidad Nacional de Colombia
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dc.publisher.faculty.spa.fl_str_mv	Facultad de Medicina
dc.publisher.place.spa.fl_str_mv	Bogotá, Colombia
dc.publisher.branch.spa.fl_str_mv	Universidad Nacional de Colombia - Sede Bogotá
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spelling	Atribución-NoComercial-CompartirIgual 4.0 Internacionalhttp://creativecommons.org/licenses/by-nc-sa/4.0/info:eu-repo/semantics/openAccesshttp://purl.org/coar/access_right/c_abf2Echeverry Gaitán, María Clarae040dbadd72121efdf7220643864e808Cadavid Gutiérrez, Luis Fernando3e6f3be0eb3276e983569e7157676dbbVargas León, Carolina María2d251fe2bebfdc40c56f3249abcd701a600Infecciones y Salud en El Trópico2022-01-11T21:18:30Z2022-01-11T21:18:30Z2021https://repositorio.unal.edu.co/handle/unal/80802Universidad Nacional de ColombiaRepositorio Institucional Universidad Nacional de Colombiahttps://repositorio.unal.edu.co/ilustraciones, gráficas, tablasLa leishmaniasis es una enfermedad de transmisión vectorial producida por parásitos del género Leishmania. Esta enfermedad presenta tres manifestaciones clínicas: Leishmaniasis cutánea (LC), Leishmaniasis mucosa (LM) y Leishmaniasis visceral. LC se caracteriza por la aparición de pápulas y úlceras en la piel, mientras LM está dada por la aparición de úlceras en la cavidad oral o nasofaríngea; LM suele estar antecedida por LC, por lo que algunos autores consideran la LM como una progresión o complicación de la enfermedad. Si bien las razones por las cuales se produce LM aún no son del todo claras, se ha evidenciado que la presencia de Leishmania RNA Virus 1 (LRV1) en la cepa infectante de Leishmania se asocia con el desarrollo de LM, se ha planteado que el reconocimiento de LRV1 por el receptor de reconocimiento de patrones (PRR) endosomal Toll-like receptor 3 (TLR3) induce la activación de una respuesta inmune antiviral que favorece la persistencia y diseminación del parásito en el hospedero. El gen que codifica para TLR3 presenta varios polimorfismos de único nucleótido (SNPs) que se han visto asociados a resistencia o susceptibilidad frente a diversas infecciones virales. La presente investigación evaluó si los SNPs de TLR3 en población colombiana se asocian con el desarrollo de LM, ya sea en contexto de infección simple por Leishmania spp. o en coinfección Leishmania spp. – LRV1. Se efectuó un estudio retrospectivo de casos y controles, en donde se genotipificaron los exones 2, 3 y 4 del gen TLR3. Se analizó la presencia de polimorfismos en este grupo de exones en una población colombiana compuesta por 60 controles (muestras de pacientes diagnosticados con LC y sin complicación mucosa) y 27 casos (muestras de pacientes diagnosticados con LM) y mediante comparación de las frecuencias alélicas y genotípicas en cada grupo se evaluó la potencial asociación entre los SNPs y el desenlace clínico de la enfermedad. Adicionalmente, se evaluaron otras variables que pudiesen asociarse con el desarrollo de LM como lo son: sexo, edad, tratamiento, entre otras, y se evaluó la estructura génica de TLR3 en la población colombiana; para esta última, se contrastó con la estructura génica de otras poblaciones a nivel mundial como población europea, asiática y africana, además de analizar su comportamiento en un contexto local, al contrastar los resultados obtenidos con población latinoamericana. Se observaron cuatro polimorfismos en la muestra de estudio, un SNP en el exón 2 del gen, en la región codificante para 5’UTR (rs3775296), y tres SNPs en el exón 4: dos mutaciones sinónimas (rs764010322 y rs3775290) y una mutación no sinónima (rs3775291) que induce la variación L412F en la proteína. No se encontró ninguna asociación entre estos cuatro SNPs y el desarrollo de LM al evaluarlo en contexto de infección simple ni en coinfección. Tras analizar la estructura poblacional de la muestra colombiana aquí estudiada, se encontró que el comportamiento de rs3775296, en el exón 2, y rs3775291, en el exón 4, es muy similar a lo reportado en otras poblaciones a nivel mundial (p>0,05). Por el contrario, la distribución de frecuencias de los polimorfismos rs764010322 y rs3775291 del exón 4, si evidenció diferencias significativas frente a otras poblaciones (p<0,001). Estas diferencias están dadas porque, para la variación rs764010322, se evidenció una mayor frecuencia de aparición de ésta variación en la muestra de estudio que en otras poblaciones a nivel global y para rs3775291, se presentó la ausencia de uno de los tres alelos posibles que se han reportado para esta variación. Finalmente, se analizaron otras variables que pudieran estar asociadas con el desarrollo de la LM y se ratificó la asociación entre está y la presencia de LRV1+ y con la variable tratamiento para LC. (Texto tomado de la fuente).Leishmaniasis is a vector-borne disease produced by Leishmania parasites with three main clinical forms of the disease, cutaneous (CL), mucosal (ML), and visceral Leishmaniasis. CL causes skin lesions, papules, and ulcers, while ML causes ulcerative lesions on nasal and oropharyngeal mucosa. Usually, ML is preceded by CL, and some authors refer to it as a metastatic progression of the disease. The causes of ML remain unknown, although the presence of Leishmania RNA virus 1 (LRV1) in the parasite has been associated with the development of ML. Indeed, it has been suggested that the recognition of LRV1 by the endosomal pattern recognition receptor (PRR) TLR3 induces an antiviral response that allows the parasite’s persistence and dissemination in the host. TLR3 gene has several single nucleotide polymorphisms (SNPs) associated with resistance or susceptibility to viral infectious diseases. This work evaluated whether TLR3 SNPs are associated with ML development in infection produced by Leishmania spp. or Leishmania spp-LRV1 co-infection. The study was designed as a case-control study and TLR3 exons 2, 3, and 4 were genotyped. The presence of SNPs on TLR3 was analyzed in a Colombian population of 60 controls (CL diagnosed patients without mucosal compromise) and 27 cases (ML diagnosed patients) and the potential association between the SNPs and the clinical outcome were evaluated by comparing the allelic and genotypic frequencies for those SNPs. Other variables that could be associated with ML were also evaluated: sex, age, and treatment, among others; the genetic structure of TLR3 in the Colombian population in the context of other populations genotypes and haplotypes such as European, African, Asian, and Latin-American. Four SNPs were found between the studied sample: one exon 2, in the 5’UTR region (rs3775296), and three on exon 4 [two synonym mutations (rs764010322 y rs3775290) and one non-synonym mutation (rs3775291) that produced the L412F change in the protein]. There was no association observed between the found SNPs and the development of ML. The genetic population structure shows that rs3775296, on exon 2, and rs3775291, on exon 4, had a similar frequency to the world populations analyzed (p>0,05) while rs764010322 and rs3775291 had a significantly different frequency to world populations (p<0,001). Those differences are due to a higher frequency of rs764010322 variation and to the absence of one of the three possible alleles reported to rs3775291 into the studied population. Finally, other variables associated with the clinical development of the disease were analyzed and the association between LRV1presence and ML development was confirmed as the potential association between absent or incomplete treatment for CL event and ML appearance.Incluye anexosMaestríaMagíster en InmunologíaLa presente investigación es un estudio de asociación genotípica, definido como un estudio descriptivo, retrospectivo de casos y controles. Para el desarrollo de este estudio se genotificó el gen TLR3 de muestra provenientes de pacientes diagnosticados con Leishmaniasis cutánea (controles) y Leishmaniasis mucosa (casos). Tras la secuenciación se identificaron SNPs de dicho gen y se efectuaron análisis de asociación a partir de la frecuencias genotípicas y alélicas evidenciadas. Adicionalmente efectuó una comparación entre el comportamiento de TLR3 en la población de estudio y otras poblaciones a nivel mundial.xix, 121 páginasapplication/pdfspaUniversidad Nacional de ColombiaBogotá - Medicina - Maestría en InmunologíaDepartamento de MicrobiologíaFacultad de MedicinaBogotá, ColombiaUniversidad Nacional de Colombia - Sede Bogotá610 - Medicina y salud::616 - EnfermedadesLeishmaniasisReceptor 3 Toll-LikeLeishmaniaLeishmaniasisToll-Like Receptor 3LeishmaniaLeishmaniaLRV1TLR3Leishmaniasis mucosaLeishmaniasis cutáneaPolimorfismo de nucleótido únicoColombiars3775296rs764010322rs3775291rs3775290Mucosal leishmaniasisCutaneous leishmaniasisSingle nucleotide polymorphismIdentificación y asociación de polimorfismos de Toll-Like Receptor 3 con el desarrollo de Leishmaniasis mucosa frente a la coinfección Leishmania spp. – Leishmania RNA Virus 1Identification and association of Toll-Like Receptor 3 polymorphisms with the development of mucosal Leishmaniasis against the coinfection Leishmania spp. - Leishmania RNA Virus 1Trabajo de grado - Maestríainfo:eu-repo/semantics/masterThesisinfo:eu-repo/semantics/acceptedVersionTexthttp://purl.org/redcol/resource_type/TMBiremeEl-Bendary, M., Neamatallah, M., Elalfy, H., Besheer, T., Elkholi, A., El-Diasty, M., Elsareef, M., Zahran, M., El-Aarag, B., Gomaa, A., Elhammady, D., El-Setouhy, M., Hegazy, A., & Esmat, G. 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PLoS Pathogens, 6(4), 1–16. https://doi.org/10.1371/journal.ppat.1000871Ministerio de Ciencia Tecnología e InnovaciónUniversidad Nacional de ColombiaEstudiantesInvestigadoresMaestrosLICENSElicense.txtlicense.txttext/plain; charset=utf-84074https://repositorio.unal.edu.co/bitstream/unal/80802/1/license.txt8153f7789df02f0a4c9e079953658ab2MD51ORIGINAL1032473343.2021.pdf1032473343.2021.pdfTesis de Maestría en Inmunologíaapplication/pdf3228997https://repositorio.unal.edu.co/bitstream/unal/80802/2/1032473343.2021.pdf2d1158c59206e6ba4fc26d1246fb1f2bMD52THUMBNAIL1032473343.2021.pdf.jpg1032473343.2021.pdf.jpgGenerated Thumbnailimage/jpeg5087https://repositorio.unal.edu.co/bitstream/unal/80802/3/1032473343.2021.pdf.jpgb78b034bf354cec7c09f926dc98cadc4MD53unal/80802oai:repositorio.unal.edu.co:unal/808022024-08-01 23:10:44.314Repositorio Institucional Universidad Nacional de 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EVESURBIFBPUiBMQSBTRUNSRVRBUsONQSBHRU5FUkFMLiAqTEEgVEVTSVMgQSBQVUJMSUNBUiBERUJFIFNFUiBMQSBWRVJTScOTTiBGSU5BTCBBUFJPQkFEQS4gCgpBbCBoYWNlciBjbGljIGVuIGVsIHNpZ3VpZW50ZSBib3TDs24sIHVzdGVkIGluZGljYSBxdWUgZXN0w6EgZGUgYWN1ZXJkbyBjb24gZXN0b3MgdMOpcm1pbm9zLiBTaSB0aWVuZSBhbGd1bmEgZHVkYSBzb2JyZSBsYSBsaWNlbmNpYSwgcG9yIGZhdm9yLCBjb250YWN0ZSBjb24gZWwgYWRtaW5pc3RyYWRvciBkZWwgc2lzdGVtYS4KClVOSVZFUlNJREFEIE5BQ0lPTkFMIERFIENPTE9NQklBIC0gw5psdGltYSBtb2RpZmljYWNpw7NuIDE5LzEwLzIwMjEK

Identificación y asociación de polimorfismos de Toll-Like Receptor 3 con el desarrollo de Leishmaniasis mucosa frente a la coinfección Leishmania spp. – Leishmania RNA Virus 1

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