<i>THEMIS</i> and <i>PTPRK</i> in celiac intestinal mucosa: coexpression in disease and after <i>in vitro</i> gliadin challenge
- Autores
- Bondar, Constanza María; Plaza Izurieta, Leticia; Fernandez Jimenez, Nora; Irastorza, Iñaki; Withoff, Sebo; 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.
Facultad de Ciencias Exactas
Laboratorio de Investigaciones del Sistema Inmune - Materia
-
Ciencias Exactas
Biología
celiac disease
genetic association
THEMIS
PTPRK
gene expression - Nivel de accesibilidad
- acceso abierto
- Condiciones de uso
- http://creativecommons.org/licenses/by-nc-sa/4.0/
- Repositorio
- Institución
- Universidad Nacional de La Plata
- OAI Identificador
- oai:sedici.unlp.edu.ar:10915/123716
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<i>THEMIS</i> and <i>PTPRK</i> in celiac intestinal mucosa: coexpression in disease and after <i>in vitro</i> gliadin challengeBondar, Constanza MaríaPlaza Izurieta, LeticiaFernandez Jimenez, NoraIrastorza, IñakiWithoff, SeboWijmenga, CiscaChirdo, Fernando GabrielBilbao, Jose RamonCiencias ExactasBiologíaceliac diseasegenetic associationTHEMISPTPRKgene expressionCeliac 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, <i>thymocyte-expressed molecule involved in selection</i> (<i>THEMIS</i>) and <i>protein tyrosine phosphatase, receptor type, kappa</i> (<i>PTPRK</i>), 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. <i>THEMIS</i> showed higher expression in active CD compared with treated patients and controls, whereas <i>PTPRK</i> 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 <i>THEMIS</i>. On the other hand, we found a significant positive correlation between <i>THEMIS</i> and <i>PTPRK</i> 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.Facultad de Ciencias ExactasLaboratorio de Investigaciones del Sistema Inmune2014-03info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionArticulohttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdf358-362http://sedici.unlp.edu.ar/handle/10915/123716enginfo:eu-repo/semantics/altIdentifier/issn/1476-5438info:eu-repo/semantics/altIdentifier/issn/1018-4813info:eu-repo/semantics/altIdentifier/pmid/23820479info:eu-repo/semantics/altIdentifier/doi/10.1038/ejhg.2013.136info:eu-repo/semantics/openAccesshttp://creativecommons.org/licenses/by-nc-sa/4.0/Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International (CC BY-NC-SA 4.0)reponame:SEDICI (UNLP)instname:Universidad Nacional de La Platainstacron:UNLP2025-09-29T11:29:28Zoai:sedici.unlp.edu.ar:10915/123716Institucionalhttp://sedici.unlp.edu.ar/Universidad públicaNo correspondehttp://sedici.unlp.edu.ar/oai/snrdalira@sedici.unlp.edu.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:13292025-09-29 11:29:28.802SEDICI (UNLP) - Universidad Nacional de La Platafalse |
dc.title.none.fl_str_mv |
<i>THEMIS</i> and <i>PTPRK</i> in celiac intestinal mucosa: coexpression in disease and after <i>in vitro</i> gliadin challenge |
title |
<i>THEMIS</i> and <i>PTPRK</i> in celiac intestinal mucosa: coexpression in disease and after <i>in vitro</i> gliadin challenge |
spellingShingle |
<i>THEMIS</i> and <i>PTPRK</i> in celiac intestinal mucosa: coexpression in disease and after <i>in vitro</i> gliadin challenge Bondar, Constanza María Ciencias Exactas Biología celiac disease genetic association THEMIS PTPRK gene expression |
title_short |
<i>THEMIS</i> and <i>PTPRK</i> in celiac intestinal mucosa: coexpression in disease and after <i>in vitro</i> gliadin challenge |
title_full |
<i>THEMIS</i> and <i>PTPRK</i> in celiac intestinal mucosa: coexpression in disease and after <i>in vitro</i> gliadin challenge |
title_fullStr |
<i>THEMIS</i> and <i>PTPRK</i> in celiac intestinal mucosa: coexpression in disease and after <i>in vitro</i> gliadin challenge |
title_full_unstemmed |
<i>THEMIS</i> and <i>PTPRK</i> in celiac intestinal mucosa: coexpression in disease and after <i>in vitro</i> gliadin challenge |
title_sort |
<i>THEMIS</i> and <i>PTPRK</i> in celiac intestinal mucosa: coexpression in disease and after <i>in vitro</i> gliadin challenge |
dc.creator.none.fl_str_mv |
Bondar, Constanza María Plaza Izurieta, Leticia Fernandez Jimenez, Nora Irastorza, Iñaki Withoff, Sebo 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 Wijmenga, Cisca Chirdo, Fernando Gabriel Bilbao, Jose Ramon |
author_role |
author |
author2 |
Plaza Izurieta, Leticia Fernandez Jimenez, Nora Irastorza, Iñaki Withoff, Sebo Wijmenga, Cisca Chirdo, Fernando Gabriel Bilbao, Jose Ramon |
author2_role |
author author author author author author author |
dc.subject.none.fl_str_mv |
Ciencias Exactas Biología celiac disease genetic association THEMIS PTPRK gene expression |
topic |
Ciencias Exactas Biología celiac disease genetic association THEMIS PTPRK gene expression |
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, <i>thymocyte-expressed molecule involved in selection</i> (<i>THEMIS</i>) and <i>protein tyrosine phosphatase, receptor type, kappa</i> (<i>PTPRK</i>), 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. <i>THEMIS</i> showed higher expression in active CD compared with treated patients and controls, whereas <i>PTPRK</i> 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 <i>THEMIS</i>. On the other hand, we found a significant positive correlation between <i>THEMIS</i> and <i>PTPRK</i> 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. Facultad de Ciencias Exactas Laboratorio de Investigaciones del Sistema Inmune |
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, <i>thymocyte-expressed molecule involved in selection</i> (<i>THEMIS</i>) and <i>protein tyrosine phosphatase, receptor type, kappa</i> (<i>PTPRK</i>), 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. <i>THEMIS</i> showed higher expression in active CD compared with treated patients and controls, whereas <i>PTPRK</i> 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 <i>THEMIS</i>. On the other hand, we found a significant positive correlation between <i>THEMIS</i> and <i>PTPRK</i> 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 Articulo 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://sedici.unlp.edu.ar/handle/10915/123716 |
url |
http://sedici.unlp.edu.ar/handle/10915/123716 |
dc.language.none.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
info:eu-repo/semantics/altIdentifier/issn/1476-5438 info:eu-repo/semantics/altIdentifier/issn/1018-4813 info:eu-repo/semantics/altIdentifier/pmid/23820479 info:eu-repo/semantics/altIdentifier/doi/10.1038/ejhg.2013.136 |
dc.rights.none.fl_str_mv |
info:eu-repo/semantics/openAccess http://creativecommons.org/licenses/by-nc-sa/4.0/ Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International (CC BY-NC-SA 4.0) |
eu_rights_str_mv |
openAccess |
rights_invalid_str_mv |
http://creativecommons.org/licenses/by-nc-sa/4.0/ Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International (CC BY-NC-SA 4.0) |
dc.format.none.fl_str_mv |
application/pdf 358-362 |
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