Identification of genetic susceptibility loci for intestinal Behçet’s disease View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2017-12

AUTHORS

Seung Won Kim, Yoon Suk Jung, Jae Bum Ahn, Eun-Soon Shin, Hui Won Jang, Hyun Jung Lee, Tae Il Kim, Do Young Kim, Dongsik Bang, Won Ho Kim, Jae Hee Cheon

ABSTRACT

Several recent genome-wide association studies (GWAS) identified susceptibility loci/genes for Behçet's disease (BD). However, no study has specifically investigated the genetic susceptibility loci associated with intestinal involvement in BD. We aimed to identify distinctive genetic susceptibility loci/genes associated with intestinal involvement in BD and determine their roles in intestinal inflammation as well as their interactions with genes involved in inflammatory bowel disease (IBD). GWAS and validation studies showed intestinal BD-specific associations with an NAALADL2 gene locus (rs3914501, P = 3.8 × 10-4) and a YIPF7 gene locus (rs6838327, P = 3.5 × 10-4). Validation, haplotype, and pathway analyses showed distinct genetic architectures between intestinal BD and BD without intestinal involvement. Furthermore, network analysis revealed shared pathogenic pathways between intestinal BD and IBD. Gene functional analyses indicated that down-regulation of NAALADL2 and YIPF7 expression was associated with exacerbating intestinal inflammatory responses both in vitro and in vivo. Our results provide new insights into intestinal BD-specific genetic variations, which represents a distinct pathway from BD without intestinal involvement. Functional consequences of the intestinal BD-specific NAALADL2 and YIPF7 expression patterns proved a suggestive association with intestinal inflammation risk, which warrants further validation. More... »

PAGES

39850

References to SciGraph publications

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URI

http://scigraph.springernature.com/pub.10.1038/srep39850

DOI

http://dx.doi.org/10.1038/srep39850

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1030898582

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/28045058


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    "description": "Several recent genome-wide association studies (GWAS) identified susceptibility loci/genes for Beh\u00e7et's disease (BD). However, no study has specifically investigated the genetic susceptibility loci associated with intestinal involvement in BD. We aimed to identify distinctive genetic susceptibility loci/genes associated with intestinal involvement in BD and determine their roles in intestinal inflammation as well as their interactions with genes involved in inflammatory bowel disease (IBD). GWAS and validation studies showed intestinal BD-specific associations with an NAALADL2 gene locus (rs3914501, P\u2009=\u20093.8\u2009\u00d7\u200910-4) and a YIPF7 gene locus (rs6838327, P\u2009=\u20093.5\u2009\u00d7\u200910-4). Validation, haplotype, and pathway analyses showed distinct genetic architectures between intestinal BD and BD without intestinal involvement. Furthermore, network analysis revealed shared pathogenic pathways between intestinal BD and IBD. Gene functional analyses indicated that down-regulation of NAALADL2 and YIPF7 expression was associated with exacerbating intestinal inflammatory responses both in vitro and in vivo. Our results provide new insights into intestinal BD-specific genetic variations, which represents a distinct pathway from BD without intestinal involvement. Functional consequences of the intestinal BD-specific NAALADL2 and YIPF7 expression patterns proved a suggestive association with intestinal inflammation risk, which warrants further validation.", 
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