dc.contributor.author | Santín Gómez, Izortze | |
dc.contributor.author | Jauregi Miguel, Amaia | |
dc.contributor.author | Velayos Gainza, Teresa | |
dc.contributor.author | Castellanos Rubio, Ainara | |
dc.contributor.author | García Etxebarria, Koldo | |
dc.contributor.author | Romero Garmendia, Irati | |
dc.contributor.author | Fernández Jiménez, Nora ![ORCID](/themes/Mirage2//images/orcid_16x16.png) | |
dc.contributor.author | Irastorza Terradillos, Iñaki Xarles ![ORCID](/themes/Mirage2//images/orcid_16x16.png) | |
dc.contributor.author | Castaño González, Luis Antonio ![ORCID](/themes/Mirage2//images/orcid_16x16.png) | |
dc.contributor.author | Bilbao Catalá, José Ramón ![ORCID](/themes/Mirage2//images/orcid_16x16.png) | |
dc.date.accessioned | 2024-02-08T11:13:37Z | |
dc.date.available | 2024-02-08T11:13:37Z | |
dc.date.issued | 2018-08-01 | |
dc.identifier.citation | Journal of Pediatric Gastroenterology and Nutrition 67(2) : 225-231 (2018) | |
dc.identifier.issn | 0277-2116 | |
dc.identifier.uri | http://hdl.handle.net/10810/65485 | |
dc.description.abstract | Objective:
The aim of the study is to identify additional celiac disease associated loci in the major histocompatibility complex (MHC) independent from classical HLA risk alleles (HLA-DR3-DQ2) and to characterize their potential functional impact in celiac disease pathogenesis at the intestinal level.
Methods:
We performed a high-resolution single-nucleotide polymorphism (SNP) genotyping of the MHC region, comparing HLA-DR3 homozygous celiac patients and non-celiac controls carrying a single copy of the B8-DR3-DQ2 conserved extended haplotype. Expression level of potential novel risk genes was determined by RT-PCR in intestinal biopsies and in intestinal and immune cells isolated from control and celiac individuals. Small interfering RNA-driven silencing of selected genes was performed in the intestinal cell line T84.
Results:
MHC genotyping revealed 2 associated SNPs, one located in TRIM27 gene and another in the non-coding gene HCG14. After stratification analysis, only HCG14 showed significant association independent from HLA-DR-DQ loci. Expression of HCG14 was slightly downregulated in epithelial cells isolated from duodenal biopsies of celiac patients, and eQTL analysis revealed that polymorphisms in HCG14 region were associated with decreased NOD1 expression in duodenal intestinal cells.
Conclusions:
We have successfully employed a conserved extended haplotype-matching strategy and identified a novel additional celiac disease risk variant in the lncRNA HCG14. This lncRNA seems to regulate the expression of NOD1 in an allele-specific manner. Further functional studies are needed to clarify the role of HCG14 in the regulation of gene expression and to determine the molecular mechanisms by which the risk variant in HCG14 contributes to celiac disease pathogenesis. | |
dc.description.sponsorship | I.R.G. and A.J.M. are supported by Predoctoral Fellowship grants from the UPV/EHU and the Basque Department of Education, respectively. N.F.J. is a Postdoctoral Fellow supported by the Basque Department of Education. A.C.R. is an Ikerbasque Research Fellow. J.R.B. is funded by Project ISCIII-PI16/00258 and co-funded by the European Union ERDF/ESF “A way to make Europe.” I.S.G. is funded by a Research Project Grant 2015111068 of the Basque Department of Health. | |
dc.language.iso | eng | es_ES |
dc.publisher | Wiley | |
dc.rights | info:eu-repo/semantics/openAccess | es_ES |
dc.title | Celiac Diasease-associated lncRNA Named HCG14 Regulates NOD1 Expression in Intestinal Cells | es_ES |
dc.type | info:eu-repo/semantics/article | es_ES |
dc.rights.holder | © 2018 by European Society for European Society for Pediatric Gastroenterology, Hepatology, and Nutrition and North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition | * |
dc.relation.publisherversion | https://onlinelibrary.wiley.com/doi/10.1097/MPG.0000000000001970 | |
dc.identifier.doi | 10.1097/MPG.0000000000001970 | |
dc.departamentoes | Bioquímica y biología molecular | es_ES |
dc.departamentoes | Genética, antropología física y fisiología animal | |
dc.departamentoeu | Biokimika eta biologia molekularra | es_ES |
dc.departamentoeu | Genetika,antropologia fisikoa eta animalien fisiologia | |
dc.identifier.eissn | 1536-4801 | |