Association of IL4R-rs1805016 and IL6R-rs8192284 polymorphisms with clinical dengue in children from Colombian populations

ABSTRACT: Background: Etiologic studies provide evidence that IL-4R and IL-6R receptors may play important roles in the regulatory mechanisms of the development of clinical dengue, especially in children which is a segment of the population with high severe dengue risk. Moreover, the allele frequenc...

Full description

Autores:
Bedoya Berrío, Gabriel de Jesús
Useche Salvador, Yerly Magnolia
Gallego Lopera, Berta Natalia
Salgado García, Doris Martha
Narváez Rojas, Carlos Fernando
Campo Nieto, Omer
Tipo de recurso:
Article of investigation
Fecha de publicación:
2019
Institución:
Universidad de Antioquia
Repositorio:
Repositorio UdeA
Idioma:
eng
OAI Identifier:
oai:bibliotecadigital.udea.edu.co:10495/42107
Acceso en línea:
https://hdl.handle.net/10495/42107
Palabra clave:
Estudios de Casos y Controles
Case-Control Studies
Dengue
Frecuencia de los Genes
Gene Frequency
Estudios de Asociación Genética
Genetic Association Studies
Predisposición Genética a la Enfermedad
Genetic Predisposition to Disease
Genotipo
Genotype
Subunidad alfa del Receptor de Interleucina-4
Interleukin-4 Receptor alpha Subunit
Reacción en Cadena de la Polimerasa
Polymerase Chain Reaction
Polimorfismo de Longitud del Fragmento de Restricción
Polymorphism, Restriction Fragment Length
Polimorfismo de Nucleótido Simple
Polymorphism, Single Nucleotide
Receptores de Interleucina-6
Receptors, Interleukin-6
Colombia - epidemiología
Colombia - epidemiology
https://id.nlm.nih.gov/mesh/D016022
https://id.nlm.nih.gov/mesh/D003715
https://id.nlm.nih.gov/mesh/D005787
https://id.nlm.nih.gov/mesh/D056726
https://id.nlm.nih.gov/mesh/D020022
https://id.nlm.nih.gov/mesh/D005838
https://id.nlm.nih.gov/mesh/D053662
https://id.nlm.nih.gov/mesh/D016133
https://id.nlm.nih.gov/mesh/D012150
https://id.nlm.nih.gov/mesh/D020641
https://id.nlm.nih.gov/mesh/D019947
https://id.nlm.nih.gov/mesh/D003105
Rights
openAccess
License
http://creativecommons.org/licenses/by-nc-nd/2.5/co/
id UDEA2_8e3ca4c7eb85a56154d3405f5d354217
oai_identifier_str oai:bibliotecadigital.udea.edu.co:10495/42107
network_acronym_str UDEA2
network_name_str Repositorio UdeA
repository_id_str
dc.title.spa.fl_str_mv Association of IL4R-rs1805016 and IL6R-rs8192284 polymorphisms with clinical dengue in children from Colombian populations
title Association of IL4R-rs1805016 and IL6R-rs8192284 polymorphisms with clinical dengue in children from Colombian populations
spellingShingle Association of IL4R-rs1805016 and IL6R-rs8192284 polymorphisms with clinical dengue in children from Colombian populations
Estudios de Casos y Controles
Case-Control Studies
Dengue
Frecuencia de los Genes
Gene Frequency
Estudios de Asociación Genética
Genetic Association Studies
Predisposición Genética a la Enfermedad
Genetic Predisposition to Disease
Genotipo
Genotype
Subunidad alfa del Receptor de Interleucina-4
Interleukin-4 Receptor alpha Subunit
Reacción en Cadena de la Polimerasa
Polymerase Chain Reaction
Polimorfismo de Longitud del Fragmento de Restricción
Polymorphism, Restriction Fragment Length
Polimorfismo de Nucleótido Simple
Polymorphism, Single Nucleotide
Receptores de Interleucina-6
Receptors, Interleukin-6
Colombia - epidemiología
Colombia - epidemiology
https://id.nlm.nih.gov/mesh/D016022
https://id.nlm.nih.gov/mesh/D003715
https://id.nlm.nih.gov/mesh/D005787
https://id.nlm.nih.gov/mesh/D056726
https://id.nlm.nih.gov/mesh/D020022
https://id.nlm.nih.gov/mesh/D005838
https://id.nlm.nih.gov/mesh/D053662
https://id.nlm.nih.gov/mesh/D016133
https://id.nlm.nih.gov/mesh/D012150
https://id.nlm.nih.gov/mesh/D020641
https://id.nlm.nih.gov/mesh/D019947
https://id.nlm.nih.gov/mesh/D003105
title_short Association of IL4R-rs1805016 and IL6R-rs8192284 polymorphisms with clinical dengue in children from Colombian populations
title_full Association of IL4R-rs1805016 and IL6R-rs8192284 polymorphisms with clinical dengue in children from Colombian populations
title_fullStr Association of IL4R-rs1805016 and IL6R-rs8192284 polymorphisms with clinical dengue in children from Colombian populations
title_full_unstemmed Association of IL4R-rs1805016 and IL6R-rs8192284 polymorphisms with clinical dengue in children from Colombian populations
title_sort Association of IL4R-rs1805016 and IL6R-rs8192284 polymorphisms with clinical dengue in children from Colombian populations
dc.creator.fl_str_mv Bedoya Berrío, Gabriel de Jesús
Useche Salvador, Yerly Magnolia
Gallego Lopera, Berta Natalia
Salgado García, Doris Martha
Narváez Rojas, Carlos Fernando
Campo Nieto, Omer
dc.contributor.author.none.fl_str_mv Bedoya Berrío, Gabriel de Jesús
Useche Salvador, Yerly Magnolia
Gallego Lopera, Berta Natalia
Salgado García, Doris Martha
Narváez Rojas, Carlos Fernando
Campo Nieto, Omer
dc.contributor.researchgroup.spa.fl_str_mv Genética Molecular (GENMOL)
dc.subject.decs.none.fl_str_mv Estudios de Casos y Controles
Case-Control Studies
Dengue
Frecuencia de los Genes
Gene Frequency
Estudios de Asociación Genética
Genetic Association Studies
Predisposición Genética a la Enfermedad
Genetic Predisposition to Disease
Genotipo
Genotype
Subunidad alfa del Receptor de Interleucina-4
Interleukin-4 Receptor alpha Subunit
Reacción en Cadena de la Polimerasa
Polymerase Chain Reaction
Polimorfismo de Longitud del Fragmento de Restricción
Polymorphism, Restriction Fragment Length
Polimorfismo de Nucleótido Simple
Polymorphism, Single Nucleotide
Receptores de Interleucina-6
Receptors, Interleukin-6
Colombia - epidemiología
Colombia - epidemiology
topic Estudios de Casos y Controles
Case-Control Studies
Dengue
Frecuencia de los Genes
Gene Frequency
Estudios de Asociación Genética
Genetic Association Studies
Predisposición Genética a la Enfermedad
Genetic Predisposition to Disease
Genotipo
Genotype
Subunidad alfa del Receptor de Interleucina-4
Interleukin-4 Receptor alpha Subunit
Reacción en Cadena de la Polimerasa
Polymerase Chain Reaction
Polimorfismo de Longitud del Fragmento de Restricción
Polymorphism, Restriction Fragment Length
Polimorfismo de Nucleótido Simple
Polymorphism, Single Nucleotide
Receptores de Interleucina-6
Receptors, Interleukin-6
Colombia - epidemiología
Colombia - epidemiology
https://id.nlm.nih.gov/mesh/D016022
https://id.nlm.nih.gov/mesh/D003715
https://id.nlm.nih.gov/mesh/D005787
https://id.nlm.nih.gov/mesh/D056726
https://id.nlm.nih.gov/mesh/D020022
https://id.nlm.nih.gov/mesh/D005838
https://id.nlm.nih.gov/mesh/D053662
https://id.nlm.nih.gov/mesh/D016133
https://id.nlm.nih.gov/mesh/D012150
https://id.nlm.nih.gov/mesh/D020641
https://id.nlm.nih.gov/mesh/D019947
https://id.nlm.nih.gov/mesh/D003105
dc.subject.meshuri.none.fl_str_mv https://id.nlm.nih.gov/mesh/D016022
https://id.nlm.nih.gov/mesh/D003715
https://id.nlm.nih.gov/mesh/D005787
https://id.nlm.nih.gov/mesh/D056726
https://id.nlm.nih.gov/mesh/D020022
https://id.nlm.nih.gov/mesh/D005838
https://id.nlm.nih.gov/mesh/D053662
https://id.nlm.nih.gov/mesh/D016133
https://id.nlm.nih.gov/mesh/D012150
https://id.nlm.nih.gov/mesh/D020641
https://id.nlm.nih.gov/mesh/D019947
https://id.nlm.nih.gov/mesh/D003105
description ABSTRACT: Background: Etiologic studies provide evidence that IL-4R and IL-6R receptors may play important roles in the regulatory mechanisms of the development of clinical dengue, especially in children which is a segment of the population with high severe dengue risk. Moreover, the allele frequencies and genetic associations may be influenced by the populational genetic background. Therefore, we performed a case-control study to evaluate possible associations between SNPs in IL4R and IL6R genes and clinical dengue in children from two Colombian populations. Methods: We genotyped the rs1805016 (IL4R) and rs8192284 (IL6R) by PCR-RFLP method, in 298 symptomatic children and 648 asymptomatic controls. Three individual genetic ancestral proportions (APs) (European, Amerindian, African) were inferred by genotyping 29 AIMs (Ancestry informative markers). The variables gender, APs, and the population of origin were used like confusion variables. Results: We found IL4R-rs1805016 GG genotype and G-allele carriers and IL6R-rs8192284 AA genotype associated with clinical dengue in the pooled and Huila samples. Nevertheless, we found no association of these polymorphisms in the sample of Antioquia. Conclusions: For the first time, we report SNPs in IL4R and IL6R genes associated with clinical dengue, which contributes to understanding the genetic susceptibility to dengue disease. Moreover, these results may be influenced by genetic background and must be evaluated through functional analysis.
publishDate 2019
dc.date.issued.none.fl_str_mv 2019
dc.date.accessioned.none.fl_str_mv 2024-09-14T16:44:55Z
dc.date.available.none.fl_str_mv 2024-09-14T16:44:55Z
dc.type.spa.fl_str_mv Artículo de investigación
dc.type.coar.spa.fl_str_mv http://purl.org/coar/resource_type/c_2df8fbb1
dc.type.redcol.spa.fl_str_mv https://purl.org/redcol/resource_type/ART
dc.type.coarversion.spa.fl_str_mv http://purl.org/coar/version/c_970fb48d4fbd8a85
dc.type.driver.spa.fl_str_mv info:eu-repo/semantics/article
dc.type.version.spa.fl_str_mv info:eu-repo/semantics/publishedVersion
format http://purl.org/coar/resource_type/c_2df8fbb1
status_str publishedVersion
dc.identifier.citation.spa.fl_str_mv Useche YM, Restrepo BN, Salgado DM, Narváez CF, Campo O, Bedoya G. Association of IL4R-rs1805016 and IL6R-rs8192284 polymorphisms with clinical dengue in children from Colombian populations. J Infect Public Health. 2019 Jan-Feb;12(1):43-48. doi: 10.1016/j.jiph.2018.08.009. Epub 2018 Sep 15. PMID: 30228077.
dc.identifier.issn.none.fl_str_mv 1876-0341
dc.identifier.uri.none.fl_str_mv https://hdl.handle.net/10495/42107
dc.identifier.doi.none.fl_str_mv 10.1016/j.jiph.2018.08.009
dc.identifier.eissn.none.fl_str_mv 1876-035X
identifier_str_mv Useche YM, Restrepo BN, Salgado DM, Narváez CF, Campo O, Bedoya G. Association of IL4R-rs1805016 and IL6R-rs8192284 polymorphisms with clinical dengue in children from Colombian populations. J Infect Public Health. 2019 Jan-Feb;12(1):43-48. doi: 10.1016/j.jiph.2018.08.009. Epub 2018 Sep 15. PMID: 30228077.
1876-0341
10.1016/j.jiph.2018.08.009
1876-035X
url https://hdl.handle.net/10495/42107
dc.language.iso.spa.fl_str_mv eng
language eng
dc.relation.ispartofjournalabbrev.spa.fl_str_mv J. Infect. Public. Health.
dc.relation.citationendpage.spa.fl_str_mv 48
dc.relation.citationissue.spa.fl_str_mv 1
dc.relation.citationstartpage.spa.fl_str_mv 43
dc.relation.citationvolume.spa.fl_str_mv 12
dc.relation.ispartofjournal.spa.fl_str_mv Journal of Infection and Public Health
dc.rights.uri.*.fl_str_mv http://creativecommons.org/licenses/by-nc-nd/2.5/co/
dc.rights.uri.spa.fl_str_mv https://creativecommons.org/licenses/by-nc-nd/4.0/
dc.rights.accessrights.spa.fl_str_mv info:eu-repo/semantics/openAccess
dc.rights.coar.spa.fl_str_mv http://purl.org/coar/access_right/c_abf2
rights_invalid_str_mv http://creativecommons.org/licenses/by-nc-nd/2.5/co/
https://creativecommons.org/licenses/by-nc-nd/4.0/
http://purl.org/coar/access_right/c_abf2
eu_rights_str_mv openAccess
dc.format.extent.spa.fl_str_mv 6 páginas
dc.format.mimetype.spa.fl_str_mv application/pdf
dc.publisher.spa.fl_str_mv Elsevier
dc.publisher.place.spa.fl_str_mv Londres, Inglaterra
institution Universidad de Antioquia
bitstream.url.fl_str_mv https://bibliotecadigital.udea.edu.co/bitstreams/21ec3bc6-380b-4cfe-b3ec-e232dec69f5e/download
https://bibliotecadigital.udea.edu.co/bitstreams/82eab4ee-cf0c-47af-afc9-55eaab84d759/download
https://bibliotecadigital.udea.edu.co/bitstreams/1cbbbc8c-1ca1-4e87-ba45-9f33c3616886/download
https://bibliotecadigital.udea.edu.co/bitstreams/cbd04355-a4d4-4032-8a00-fed699256b71/download
https://bibliotecadigital.udea.edu.co/bitstreams/ae88ed9e-2a5d-4e7c-8491-11a82a372bad/download
bitstream.checksum.fl_str_mv 06b579e3fc622812ebf36c9eed67dcba
b88b088d9957e670ce3b3fbe2eedbc13
8a4605be74aa9ea9d79846c1fba20a33
30ef712fe71600f5671a52917395087e
7bfce5e2914a63f359edcb5f9b50c1ab
bitstream.checksumAlgorithm.fl_str_mv MD5
MD5
MD5
MD5
MD5
repository.name.fl_str_mv Repositorio Institucional de la Universidad de Antioquia
repository.mail.fl_str_mv aplicacionbibliotecadigitalbiblioteca@udea.edu.co
_version_ 1851052276890730496
spelling Bedoya Berrío, Gabriel de JesúsUseche Salvador, Yerly MagnoliaGallego Lopera, Berta NataliaSalgado García, Doris MarthaNarváez Rojas, Carlos FernandoCampo Nieto, OmerGenética Molecular (GENMOL)2024-09-14T16:44:55Z2024-09-14T16:44:55Z2019Useche YM, Restrepo BN, Salgado DM, Narváez CF, Campo O, Bedoya G. Association of IL4R-rs1805016 and IL6R-rs8192284 polymorphisms with clinical dengue in children from Colombian populations. J Infect Public Health. 2019 Jan-Feb;12(1):43-48. doi: 10.1016/j.jiph.2018.08.009. Epub 2018 Sep 15. PMID: 30228077.1876-0341https://hdl.handle.net/10495/4210710.1016/j.jiph.2018.08.0091876-035XABSTRACT: Background: Etiologic studies provide evidence that IL-4R and IL-6R receptors may play important roles in the regulatory mechanisms of the development of clinical dengue, especially in children which is a segment of the population with high severe dengue risk. Moreover, the allele frequencies and genetic associations may be influenced by the populational genetic background. Therefore, we performed a case-control study to evaluate possible associations between SNPs in IL4R and IL6R genes and clinical dengue in children from two Colombian populations. Methods: We genotyped the rs1805016 (IL4R) and rs8192284 (IL6R) by PCR-RFLP method, in 298 symptomatic children and 648 asymptomatic controls. Three individual genetic ancestral proportions (APs) (European, Amerindian, African) were inferred by genotyping 29 AIMs (Ancestry informative markers). The variables gender, APs, and the population of origin were used like confusion variables. Results: We found IL4R-rs1805016 GG genotype and G-allele carriers and IL6R-rs8192284 AA genotype associated with clinical dengue in the pooled and Huila samples. Nevertheless, we found no association of these polymorphisms in the sample of Antioquia. Conclusions: For the first time, we report SNPs in IL4R and IL6R genes associated with clinical dengue, which contributes to understanding the genetic susceptibility to dengue disease. Moreover, these results may be influenced by genetic background and must be evaluated through functional analysis.Colombia. Ministerio de Ciencia, Tecnología e Innovación - MinCienciasCOL00067236 páginasapplication/pdfengElsevierLondres, Inglaterrahttp://creativecommons.org/licenses/by-nc-nd/2.5/co/https://creativecommons.org/licenses/by-nc-nd/4.0/info:eu-repo/semantics/openAccesshttp://purl.org/coar/access_right/c_abf2Association of IL4R-rs1805016 and IL6R-rs8192284 polymorphisms with clinical dengue in children from Colombian populationsArtículo de investigaciónhttp://purl.org/coar/resource_type/c_2df8fbb1https://purl.org/redcol/resource_type/ARThttp://purl.org/coar/version/c_970fb48d4fbd8a85info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionEstudios de Casos y ControlesCase-Control StudiesDengueFrecuencia de los GenesGene FrequencyEstudios de Asociación GenéticaGenetic Association StudiesPredisposición Genética a la EnfermedadGenetic Predisposition to DiseaseGenotipoGenotypeSubunidad alfa del Receptor de Interleucina-4Interleukin-4 Receptor alpha SubunitReacción en Cadena de la PolimerasaPolymerase Chain ReactionPolimorfismo de Longitud del Fragmento de RestricciónPolymorphism, Restriction Fragment LengthPolimorfismo de Nucleótido SimplePolymorphism, Single NucleotideReceptores de Interleucina-6Receptors, Interleukin-6Colombia - epidemiologíaColombia - epidemiologyhttps://id.nlm.nih.gov/mesh/D016022https://id.nlm.nih.gov/mesh/D003715https://id.nlm.nih.gov/mesh/D005787https://id.nlm.nih.gov/mesh/D056726https://id.nlm.nih.gov/mesh/D020022https://id.nlm.nih.gov/mesh/D005838https://id.nlm.nih.gov/mesh/D053662https://id.nlm.nih.gov/mesh/D016133https://id.nlm.nih.gov/mesh/D012150https://id.nlm.nih.gov/mesh/D020641https://id.nlm.nih.gov/mesh/D019947https://id.nlm.nih.gov/mesh/D003105J. Infect. Public. Health.4814312Journal of Infection and Public HealthPrograma Nacional en Ciencias BásicasMinCiencias 1115-493-26145; Contract 441.2009RoR:03fd5ne08PublicationORIGINALBedoyaGabriel_2019_Association_Dengue_Children.pdfBedoyaGabriel_2019_Association_Dengue_Children.pdfArtículo de investigaciónapplication/pdf842982https://bibliotecadigital.udea.edu.co/bitstreams/21ec3bc6-380b-4cfe-b3ec-e232dec69f5e/download06b579e3fc622812ebf36c9eed67dcbaMD51trueAnonymousREADCC-LICENSElicense_rdflicense_rdfapplication/rdf+xml; charset=utf-8823https://bibliotecadigital.udea.edu.co/bitstreams/82eab4ee-cf0c-47af-afc9-55eaab84d759/downloadb88b088d9957e670ce3b3fbe2eedbc13MD52falseAnonymousREADLICENSElicense.txtlicense.txttext/plain; charset=utf-81748https://bibliotecadigital.udea.edu.co/bitstreams/1cbbbc8c-1ca1-4e87-ba45-9f33c3616886/download8a4605be74aa9ea9d79846c1fba20a33MD53falseAnonymousREADTEXTBedoyaGabriel_2019_Association_Dengue_Children.pdf.txtBedoyaGabriel_2019_Association_Dengue_Children.pdf.txtExtracted texttext/plain80059https://bibliotecadigital.udea.edu.co/bitstreams/cbd04355-a4d4-4032-8a00-fed699256b71/download30ef712fe71600f5671a52917395087eMD54falseAnonymousREADTHUMBNAILBedoyaGabriel_2019_Association_Dengue_Children.pdf.jpgBedoyaGabriel_2019_Association_Dengue_Children.pdf.jpgGenerated Thumbnailimage/jpeg15185https://bibliotecadigital.udea.edu.co/bitstreams/ae88ed9e-2a5d-4e7c-8491-11a82a372bad/download7bfce5e2914a63f359edcb5f9b50c1abMD55falseAnonymousREAD10495/42107oai:bibliotecadigital.udea.edu.co:10495/421072025-03-26 19:45:00.497http://creativecommons.org/licenses/by-nc-nd/2.5/co/open.accesshttps://bibliotecadigital.udea.edu.coRepositorio Institucional de la Universidad de Antioquiaaplicacionbibliotecadigitalbiblioteca@udea.edu.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