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Identification of OCTN2 variants and their association with phenotypes of Crohn’s disease in a Korean population

Crohn’s disease (CD) is a chronic inflammatory bowel disease and a genetic variant in the OCTN2, g.-207G > C is significantly associated with CD susceptibility. This study was aimed to identify novel OCTN2 functional promoter variants and their roles in transcriptional regulation using various in...

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Autores principales: Park, Hyo Jin, Jung, Eun Suk, Kong, Kyoung Ae, Park, Eun-Mi, Cheon, Jae Hee, Choi, Ji Ha
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4786794/
https://www.ncbi.nlm.nih.gov/pubmed/26965072
http://dx.doi.org/10.1038/srep22887
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author Park, Hyo Jin
Jung, Eun Suk
Kong, Kyoung Ae
Park, Eun-Mi
Cheon, Jae Hee
Choi, Ji Ha
author_facet Park, Hyo Jin
Jung, Eun Suk
Kong, Kyoung Ae
Park, Eun-Mi
Cheon, Jae Hee
Choi, Ji Ha
author_sort Park, Hyo Jin
collection PubMed
description Crohn’s disease (CD) is a chronic inflammatory bowel disease and a genetic variant in the OCTN2, g.-207G > C is significantly associated with CD susceptibility. This study was aimed to identify novel OCTN2 functional promoter variants and their roles in transcriptional regulation using various in vitro assays. In addition, we investigated the association between OCTN2 genotypes and CD through genetic analysis using DNA samples from 193 patients with CD and 281 healthy controls. Among the three major promoter haplotypes of OCTN2 identified, one haplotype, H3, showed a significant decrease in promoter activity: two polymorphisms in H3 were associated with a significant reduction in promoter activity. In particular, we found that the reduced transcriptional activity of those two polymorphisms results from a reduction in the binding affinity of the activators, NF-E2 and YY1, to the OCTN2 promoter. The functional haplotype of the OCTN2 promoter was associated with clinical course of CD such as the disease behavior and need for surgery. However, genetic variants or haplotypes of OCTN2 did not affect the susceptibility to CD. Our results suggest that a common promoter haplotype of OCTN2 regulates the transcriptional rate of OCTN2 and influences the clinical course of CD.
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spelling pubmed-47867942016-03-11 Identification of OCTN2 variants and their association with phenotypes of Crohn’s disease in a Korean population Park, Hyo Jin Jung, Eun Suk Kong, Kyoung Ae Park, Eun-Mi Cheon, Jae Hee Choi, Ji Ha Sci Rep Article Crohn’s disease (CD) is a chronic inflammatory bowel disease and a genetic variant in the OCTN2, g.-207G > C is significantly associated with CD susceptibility. This study was aimed to identify novel OCTN2 functional promoter variants and their roles in transcriptional regulation using various in vitro assays. In addition, we investigated the association between OCTN2 genotypes and CD through genetic analysis using DNA samples from 193 patients with CD and 281 healthy controls. Among the three major promoter haplotypes of OCTN2 identified, one haplotype, H3, showed a significant decrease in promoter activity: two polymorphisms in H3 were associated with a significant reduction in promoter activity. In particular, we found that the reduced transcriptional activity of those two polymorphisms results from a reduction in the binding affinity of the activators, NF-E2 and YY1, to the OCTN2 promoter. The functional haplotype of the OCTN2 promoter was associated with clinical course of CD such as the disease behavior and need for surgery. However, genetic variants or haplotypes of OCTN2 did not affect the susceptibility to CD. Our results suggest that a common promoter haplotype of OCTN2 regulates the transcriptional rate of OCTN2 and influences the clinical course of CD. Nature Publishing Group 2016-03-11 /pmc/articles/PMC4786794/ /pubmed/26965072 http://dx.doi.org/10.1038/srep22887 Text en Copyright © 2016, Macmillan Publishers Limited http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
spellingShingle Article
Park, Hyo Jin
Jung, Eun Suk
Kong, Kyoung Ae
Park, Eun-Mi
Cheon, Jae Hee
Choi, Ji Ha
Identification of OCTN2 variants and their association with phenotypes of Crohn’s disease in a Korean population
title Identification of OCTN2 variants and their association with phenotypes of Crohn’s disease in a Korean population
title_full Identification of OCTN2 variants and their association with phenotypes of Crohn’s disease in a Korean population
title_fullStr Identification of OCTN2 variants and their association with phenotypes of Crohn’s disease in a Korean population
title_full_unstemmed Identification of OCTN2 variants and their association with phenotypes of Crohn’s disease in a Korean population
title_short Identification of OCTN2 variants and their association with phenotypes of Crohn’s disease in a Korean population
title_sort identification of octn2 variants and their association with phenotypes of crohn’s disease in a korean population
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4786794/
https://www.ncbi.nlm.nih.gov/pubmed/26965072
http://dx.doi.org/10.1038/srep22887
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