title: Identification of genetic susceptibility loci for intestinal Behçet's disease.
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.
authors.affiliation: Department of Internal Medicine and Institute of Gastroenterology, Yonsei University College of Medicine, Seoul, Korea.|Severance Biomedical Science Institute, Yonsei University College of Medicine, Seoul, Korea.|Brain Korea 21 PLUS Project for Medical Science, Yonsei University College of Medicine, Seoul, Korea.
authors.forename: Seung Won
authors.initials: SW
authors.lastname: Kim
authors.affiliation: Division of Gastroenterology, Department of Internal Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Korea.
authors.forename: Yoon Suk
authors.initials: YS
authors.lastname: Jung
authors.affiliation: Department of Medicine, Yonsei University College of Medicine, Seoul, Korea.
authors.forename: Jae Bum
authors.initials: JB
authors.lastname: Ahn
authors.affiliation: Bioinformatics team, DNA Link Inc., Seoul, Korea.
authors.forename: Eun-Soon
authors.initials: ES
authors.lastname: Shin
authors.affiliation: Department of Internal Medicine and Institute of Gastroenterology, Yonsei University College of Medicine, Seoul, Korea.
authors.forename: Hui Won
authors.initials: HW
authors.lastname: Jang
authors.affiliation: Department of Internal Medicine and Institute of Gastroenterology, Yonsei University College of Medicine, Seoul, Korea.
authors.forename: Hyun Jung
authors.initials: HJ
authors.lastname: Lee
authors.affiliation: Department of Internal Medicine and Institute of Gastroenterology, Yonsei University College of Medicine, Seoul, Korea.
authors.forename: Tae
authors.initials: T
authors.lastname: Il Kim
authors.affiliation: Department of Dermatology and Cutaneous Biology Research Institute, Yonsei University College of Medicine, Seoul, Korea.
authors.forename: Do Young
authors.initials: DY
authors.lastname: Kim
authors.affiliation: Department of Dermatology, Catholic Kwandong University International St. Mary's Hospital, Seoul, Korea.
authors.forename: Dongsik
authors.initials: D
authors.lastname: Bang
authors.affiliation: Department of Internal Medicine and Institute of Gastroenterology, Yonsei University College of Medicine, Seoul, Korea.
authors.forename: Won Ho
authors.initials: WH
authors.lastname: Kim
authors.affiliation: Department of Internal Medicine and Institute of Gastroenterology, Yonsei University College of Medicine, Seoul, Korea.|Severance Biomedical Science Institute, Yonsei University College of Medicine, Seoul, Korea.|Brain Korea 21 PLUS Project for Medical Science, Yonsei University College of Medicine, Seoul, Korea.
authors.forename: Jae Hee
authors.initials: JH
authors.lastname: Cheon
mesh_terms: D000328:Adult; D001528:Behcet Syndrome / Q000235:genetics* / Q000473:pathology; D005260:Female; D043425:Glutamate Carboxypeptidase II / Q000235:genetics* / Q000378:metabolism; D019073:HT29 Cells; D006801:Humans; D007410:Intestinal Diseases / Q000235:genetics* / Q000473:pathology; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D008875:Middle Aged
chemical_list: D008565:Membrane Proteins; C000597036:NAALADL2 protein, human; C000628705:YIPF7 protein, human; D043425:Glutamate Carboxypeptidase II