THEMIS and PTPRK in celiac intestinal mucosa: Coexpression in disease and after in vitro gliadin challenge

Autores
Bondar, Constanza María; Plaza Izurieta, Leticia; Fernandez Jimenez, Nora; Irastorza, Iñaki; Withoff, Sebo; Grupo CEGEC; Wijmenga, Cisca; Chirdo, Fernando Gabriel; Bilbao, Jose Ramon
Año de publicación
2014
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Celiac disease (CD) is an immune mediated, polygenic disorder, where HLA-DQ2/DQ8 alleles contribute around 35% to genetic risk, but several other genes are also involved. Genome-wide association studies (GWASs) and the more recent immunochip genotyping projects have fine-mapped 39 regions of genetic susceptibility to the disease, most of which harbor candidate genes that could participate in this disease process. We focused our attention to the GWAS peak on chr6: 127.99–128.38 Mb, a region including two genes, thymocyte-expressed molecule involved in selection (THEMIS) and protein tyrosine phosphatase, receptor type, kappa (PTPRK), both of which have immune-related functions. The aim of this work was to evaluate the expression levels of these two genes in duodenal mucosa of active and treated CD patients and in controls, and to determine whether SNPs (rs802734, rs55743914, rs72975916, rs10484718 and rs9491896) associated with CD have any influence on gene expression. THEMIS showed higher expression in active CD compared with treated patients and controls, whereas PTPRK showed lower expression. Our study confirmed the association of this region with CD in our population, but only the genotype of rs802734 showed some influence in the expression of THEMIS. On the other hand, we found a significant positive correlation between THEMIS and PTPRK mRNA levels in CD patients but not in controls. Our results suggest a possible role for both candidate genes in CD pathogenesis and the existence of complex, regulatory relationships that reside in the vast non-coding, functional intergenic regions of the genome. Further investigation is needed to clarify the impact of the disease-associated SNPs on gene function.
Fil: Bondar, Constanza María. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Departamento de Ciencias Biológicas. Laboratorio de Investigaciones del Sistema Inmune; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Plaza Izurieta, Leticia. Universidad del País Vasco; España
Fil: Fernandez Jimenez, Nora. Universidad del País Vasco; España
Fil: Irastorza, Iñaki. Hospital Universitario Cruces; España
Fil: Withoff, Sebo. University of Groningen; Países Bajos
Fil: Grupo CEGEC. No especifica;
Fil: Wijmenga, Cisca. University of Groningen; Países Bajos
Fil: Chirdo, Fernando Gabriel. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Departamento de Ciencias Biológicas. Laboratorio de Investigaciones del Sistema Inmune; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata; Argentina
Fil: Bilbao, Jose Ramon. Universidad del País Vasco; España
Materia
Celiac Disease
Genetic Association
Themis
Ptprk
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/80538
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/80538
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling THEMIS and PTPRK in celiac intestinal mucosa: Coexpression in disease and after in vitro gliadin challengeBondar, Constanza MaríaPlaza Izurieta, LeticiaFernandez Jimenez, NoraIrastorza, IñakiWithoff, SeboGrupo CEGECWijmenga, CiscaChirdo, Fernando GabrielBilbao, Jose RamonCeliac DiseaseGenetic AssociationThemisPtprkhttps://purl.org/becyt/ford/3.1https://purl.org/becyt/ford/3Celiac disease (CD) is an immune mediated, polygenic disorder, where HLA-DQ2/DQ8 alleles contribute around 35% to genetic risk, but several other genes are also involved. Genome-wide association studies (GWASs) and the more recent immunochip genotyping projects have fine-mapped 39 regions of genetic susceptibility to the disease, most of which harbor candidate genes that could participate in this disease process. We focused our attention to the GWAS peak on chr6: 127.99–128.38 Mb, a region including two genes, thymocyte-expressed molecule involved in selection (THEMIS) and protein tyrosine phosphatase, receptor type, kappa (PTPRK), both of which have immune-related functions. The aim of this work was to evaluate the expression levels of these two genes in duodenal mucosa of active and treated CD patients and in controls, and to determine whether SNPs (rs802734, rs55743914, rs72975916, rs10484718 and rs9491896) associated with CD have any influence on gene expression. THEMIS showed higher expression in active CD compared with treated patients and controls, whereas PTPRK showed lower expression. Our study confirmed the association of this region with CD in our population, but only the genotype of rs802734 showed some influence in the expression of THEMIS. On the other hand, we found a significant positive correlation between THEMIS and PTPRK mRNA levels in CD patients but not in controls. Our results suggest a possible role for both candidate genes in CD pathogenesis and the existence of complex, regulatory relationships that reside in the vast non-coding, functional intergenic regions of the genome. Further investigation is needed to clarify the impact of the disease-associated SNPs on gene function.Fil: Bondar, Constanza María. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Departamento de Ciencias Biológicas. Laboratorio de Investigaciones del Sistema Inmune; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Plaza Izurieta, Leticia. Universidad del País Vasco; EspañaFil: Fernandez Jimenez, Nora. Universidad del País Vasco; EspañaFil: Irastorza, Iñaki. Hospital Universitario Cruces; EspañaFil: Withoff, Sebo. University of Groningen; Países BajosFil: Grupo CEGEC. No especifica;Fil: Wijmenga, Cisca. University of Groningen; Países BajosFil: Chirdo, Fernando Gabriel. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Departamento de Ciencias Biológicas. Laboratorio de Investigaciones del Sistema Inmune; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata; ArgentinaFil: Bilbao, Jose Ramon. Universidad del País Vasco; EspañaNature Publishing Group2014-03info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/80538Bondar, Constanza María; Plaza Izurieta, Leticia; Fernandez Jimenez, Nora; Irastorza, Iñaki; Withoff, Sebo; et al.; THEMIS and PTPRK in celiac intestinal mucosa: Coexpression in disease and after in vitro gliadin challenge; Nature Publishing Group; European Journal Of Human Genetics; 22; 3; 3-2014; 358-3621018-4813CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/doi/10.1038/ejhg.2013.136info:eu-repo/semantics/altIdentifier/url/https://www.nature.com/articles/ejhg2013136info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-29T10:02:40Zoai:ri.conicet.gov.ar:11336/80538instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-09-29 10:02:41.274CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv THEMIS and PTPRK in celiac intestinal mucosa: Coexpression in disease and after in vitro gliadin challenge
title THEMIS and PTPRK in celiac intestinal mucosa: Coexpression in disease and after in vitro gliadin challenge
spellingShingle THEMIS and PTPRK in celiac intestinal mucosa: Coexpression in disease and after in vitro gliadin challenge
Bondar, Constanza María
Celiac Disease
Genetic Association
Themis
Ptprk
title_short THEMIS and PTPRK in celiac intestinal mucosa: Coexpression in disease and after in vitro gliadin challenge
title_full THEMIS and PTPRK in celiac intestinal mucosa: Coexpression in disease and after in vitro gliadin challenge
title_fullStr THEMIS and PTPRK in celiac intestinal mucosa: Coexpression in disease and after in vitro gliadin challenge
title_full_unstemmed THEMIS and PTPRK in celiac intestinal mucosa: Coexpression in disease and after in vitro gliadin challenge
title_sort THEMIS and PTPRK in celiac intestinal mucosa: Coexpression in disease and after in vitro gliadin challenge
dc.creator.none.fl_str_mv Bondar, Constanza María
Plaza Izurieta, Leticia
Fernandez Jimenez, Nora
Irastorza, Iñaki
Withoff, Sebo
Grupo CEGEC
Wijmenga, Cisca
Chirdo, Fernando Gabriel
Bilbao, Jose Ramon
author Bondar, Constanza María
author_facet Bondar, Constanza María
Plaza Izurieta, Leticia
Fernandez Jimenez, Nora
Irastorza, Iñaki
Withoff, Sebo
Grupo CEGEC
Wijmenga, Cisca
Chirdo, Fernando Gabriel
Bilbao, Jose Ramon
author_role author
author2 Plaza Izurieta, Leticia
Fernandez Jimenez, Nora
Irastorza, Iñaki
Withoff, Sebo
Grupo CEGEC
Wijmenga, Cisca
Chirdo, Fernando Gabriel
Bilbao, Jose Ramon
author2_role author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Celiac Disease
Genetic Association
Themis
Ptprk
topic Celiac Disease
Genetic Association
Themis
Ptprk
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.1
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv Celiac disease (CD) is an immune mediated, polygenic disorder, where HLA-DQ2/DQ8 alleles contribute around 35% to genetic risk, but several other genes are also involved. Genome-wide association studies (GWASs) and the more recent immunochip genotyping projects have fine-mapped 39 regions of genetic susceptibility to the disease, most of which harbor candidate genes that could participate in this disease process. We focused our attention to the GWAS peak on chr6: 127.99–128.38 Mb, a region including two genes, thymocyte-expressed molecule involved in selection (THEMIS) and protein tyrosine phosphatase, receptor type, kappa (PTPRK), both of which have immune-related functions. The aim of this work was to evaluate the expression levels of these two genes in duodenal mucosa of active and treated CD patients and in controls, and to determine whether SNPs (rs802734, rs55743914, rs72975916, rs10484718 and rs9491896) associated with CD have any influence on gene expression. THEMIS showed higher expression in active CD compared with treated patients and controls, whereas PTPRK showed lower expression. Our study confirmed the association of this region with CD in our population, but only the genotype of rs802734 showed some influence in the expression of THEMIS. On the other hand, we found a significant positive correlation between THEMIS and PTPRK mRNA levels in CD patients but not in controls. Our results suggest a possible role for both candidate genes in CD pathogenesis and the existence of complex, regulatory relationships that reside in the vast non-coding, functional intergenic regions of the genome. Further investigation is needed to clarify the impact of the disease-associated SNPs on gene function.
Fil: Bondar, Constanza María. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Departamento de Ciencias Biológicas. Laboratorio de Investigaciones del Sistema Inmune; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Plaza Izurieta, Leticia. Universidad del País Vasco; España
Fil: Fernandez Jimenez, Nora. Universidad del País Vasco; España
Fil: Irastorza, Iñaki. Hospital Universitario Cruces; España
Fil: Withoff, Sebo. University of Groningen; Países Bajos
Fil: Grupo CEGEC. No especifica;
Fil: Wijmenga, Cisca. University of Groningen; Países Bajos
Fil: Chirdo, Fernando Gabriel. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Departamento de Ciencias Biológicas. Laboratorio de Investigaciones del Sistema Inmune; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata; Argentina
Fil: Bilbao, Jose Ramon. Universidad del País Vasco; España
description Celiac disease (CD) is an immune mediated, polygenic disorder, where HLA-DQ2/DQ8 alleles contribute around 35% to genetic risk, but several other genes are also involved. Genome-wide association studies (GWASs) and the more recent immunochip genotyping projects have fine-mapped 39 regions of genetic susceptibility to the disease, most of which harbor candidate genes that could participate in this disease process. We focused our attention to the GWAS peak on chr6: 127.99–128.38 Mb, a region including two genes, thymocyte-expressed molecule involved in selection (THEMIS) and protein tyrosine phosphatase, receptor type, kappa (PTPRK), both of which have immune-related functions. The aim of this work was to evaluate the expression levels of these two genes in duodenal mucosa of active and treated CD patients and in controls, and to determine whether SNPs (rs802734, rs55743914, rs72975916, rs10484718 and rs9491896) associated with CD have any influence on gene expression. THEMIS showed higher expression in active CD compared with treated patients and controls, whereas PTPRK showed lower expression. Our study confirmed the association of this region with CD in our population, but only the genotype of rs802734 showed some influence in the expression of THEMIS. On the other hand, we found a significant positive correlation between THEMIS and PTPRK mRNA levels in CD patients but not in controls. Our results suggest a possible role for both candidate genes in CD pathogenesis and the existence of complex, regulatory relationships that reside in the vast non-coding, functional intergenic regions of the genome. Further investigation is needed to clarify the impact of the disease-associated SNPs on gene function.
publishDate 2014
dc.date.none.fl_str_mv 2014-03
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/80538
Bondar, Constanza María; Plaza Izurieta, Leticia; Fernandez Jimenez, Nora; Irastorza, Iñaki; Withoff, Sebo; et al.; THEMIS and PTPRK in celiac intestinal mucosa: Coexpression in disease and after in vitro gliadin challenge; Nature Publishing Group; European Journal Of Human Genetics; 22; 3; 3-2014; 358-362
1018-4813
CONICET Digital
CONICET
url http://hdl.handle.net/11336/80538
identifier_str_mv Bondar, Constanza María; Plaza Izurieta, Leticia; Fernandez Jimenez, Nora; Irastorza, Iñaki; Withoff, Sebo; et al.; THEMIS and PTPRK in celiac intestinal mucosa: Coexpression in disease and after in vitro gliadin challenge; Nature Publishing Group; European Journal Of Human Genetics; 22; 3; 3-2014; 358-362
1018-4813
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/doi/10.1038/ejhg.2013.136
info:eu-repo/semantics/altIdentifier/url/https://www.nature.com/articles/ejhg2013136
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv Nature Publishing Group
publisher.none.fl_str_mv Nature Publishing Group
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
repository.name.fl_str_mv CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
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score 13.070432

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