<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
SEDICI (UNLP)
Institución
Universidad Nacional de La Plata
OAI Identificador
oai:sedici.unlp.edu.ar:10915/123716

id SEDICI_7538b123d6f456768c1ebe6fba3afbdb
oai_identifier_str oai:sedici.unlp.edu.ar:10915/123716
network_acronym_str SEDICI
repository_id_str 1329
network_name_str SEDICI (UNLP)
spelling <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
dc.source.none.fl_str_mv reponame:SEDICI (UNLP)
instname:Universidad Nacional de La Plata
instacron:UNLP
reponame_str SEDICI (UNLP)
collection SEDICI (UNLP)
instname_str Universidad Nacional de La Plata
instacron_str UNLP
institution UNLP
repository.name.fl_str_mv SEDICI (UNLP) - Universidad Nacional de La Plata
repository.mail.fl_str_mv alira@sedici.unlp.edu.ar
_version_ 1844616173704970240
score 13.070432