Identification of genetic susceptibility loci for intestinal Behçet's disease

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

Research output: Contribution to journalArticle

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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.

Original languageEnglish
Article number39850
JournalScientific reports
Volume7
DOIs
Publication statusPublished - 2017 Jan 3

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Intestinal Diseases
Genetic Loci
Genetic Predisposition to Disease
Genes
Genome-Wide Association Study
Inflammatory Bowel Diseases
Inflammation
Validation Studies
Haplotypes
Down-Regulation

All Science Journal Classification (ASJC) codes

  • General

Cite this

Kim, S. W., Jung, Y. S., Ahn, J. B., Shin, E. S., Jang, H. W., Lee, H. J., ... Cheon, J. H. (2017). Identification of genetic susceptibility loci for intestinal Behçet's disease. Scientific reports, 7, [39850]. https://doi.org/10.1038/srep39850
Kim, Seung Won ; Jung, Yoon Suk ; Ahn, Jae Bum ; Shin, Eun Soon ; Jang, Hui Won ; Lee, Hyun Jung ; Il Kim, Tae ; Kim, Do Young ; Bang, Dongsik ; Kim, Won Ho ; Cheon, Jae Hee. / Identification of genetic susceptibility loci for intestinal Behçet's disease. In: Scientific reports. 2017 ; Vol. 7.
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Kim, SW, Jung, YS, Ahn, JB, Shin, ES, Jang, HW, Lee, HJ, Il Kim, T, Kim, DY, Bang, D, Kim, WH & Cheon, JH 2017, 'Identification of genetic susceptibility loci for intestinal Behçet's disease', Scientific reports, vol. 7, 39850. https://doi.org/10.1038/srep39850

Identification of genetic susceptibility loci for intestinal Behçet's disease. / Kim, Seung Won; Jung, Yoon Suk; Ahn, Jae Bum; Shin, Eun Soon; Jang, Hui Won; Lee, Hyun Jung; Il Kim, Tae; Kim, Do Young; Bang, Dongsik; Kim, Won Ho; Cheon, Jae Hee.

In: Scientific reports, Vol. 7, 39850, 03.01.2017.

Research output: Contribution to journalArticle

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AU - Kim, Seung Won

AU - Jung, Yoon Suk

AU - Ahn, Jae Bum

AU - Shin, Eun Soon

AU - Jang, Hui Won

AU - Lee, Hyun Jung

AU - Il Kim, Tae

AU - Kim, Do Young

AU - Bang, Dongsik

AU - Kim, Won Ho

AU - Cheon, Jae Hee

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