title: HLA-C*01 is a Risk Factor for Crohn's Disease.
abstract: BACKGROUND
  A dysregulated mucosal immune response to the intestinal environment in a genetically susceptible host is hypothesized to be critical to the pathogenesis of Crohn's disease (CD). Therefore, we examined CD-susceptibility genes involved in the immune response through a genome-wide association study and consecutive genotyping of human leukocyte antigens (HLAs) and killer cell immunoglobulin-like receptors.
  
  
  METHODS
  An initial genome-wide association study was performed with 275 CD patients and 2369 controls from a Korean population. To validate the loci identified in the genome-wide association study, replication genotyping was performed in a different cohort of 242 CD patients and 1066 controls. Finally, high-resolution genotyping of HLA and killer cell immunoglobulin-like receptor was performed.
  
  
  RESULTS
  Four susceptibility loci, a promoter region in tumor necrosis factor (ligand) superfamily member (TNFSF15) and 3 independent regions in HLAs, showed significant associations with CD. Among them, rs114985235 in the intergenic region between HLA-B and HLA-C showed the strongest association, with an increased risk of CD (P = 8.71 × 10; odds ratio, 2.25). HLA typing in this region showed HLA-C*01 to be responsible for the association of CD among 43 HLA-B and HLA-C genotypes identified in the Korean population. However, the interaction of HLA-C with killer cell immunoglobulin-like receptor had little effect on the development of CD.
  
  
  CONCLUSIONS
  We newly identified HLA-C*01 as a prominent CD-susceptibility HLA allotype in the Korean population. In addition, these results confirm that genetic variations in immune response genes, such as HLAs and TNFSF15, are important host factors for the pathogenesis of CD.
authors.affiliation: *Department of Pharmacology, Brain Korea 21 PLUS Project for Medical Sciences, Severance Biomedical Science Institute, Yonsei University College of Medicine, Seoul, Korea; †Department of Internal Medicine and Institute of Gastroenterology, Yonsei University College of Medicine, Seoul, Korea; ‡Department of Oral Biology, College of Dentistry, Yonsei University, Seoul, Korea; §Department of Laboratory Medicine, Seoul National University College of Medicine, Seoul, Korea; ‖Hematopoietic Stem Cell Bank, College of Medicine, The Catholic University of Korea, Seoul, Korea; Departments of ¶Laboratory Medicine, and **Gastroenterology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.
authors.forename: Eun Suk
authors.initials: ES
authors.lastname: Jung
authors.forename: Jae Hee
authors.initials: JH
authors.lastname: Cheon
authors.forename: Ji Hyun
authors.initials: JH
authors.lastname: Lee
authors.forename: Soo Jung
authors.initials: SJ
authors.lastname: Park
authors.forename: Hui Won
authors.initials: HW
authors.lastname: Jang
authors.forename: Sook Hee
authors.initials: SH
authors.lastname: Chung
authors.forename: Myoung Hee
authors.initials: MH
authors.lastname: Park
authors.forename: Tai-Gyu
authors.initials: TG
authors.lastname: Kim
authors.forename: Heung-Bum
authors.initials: HB
authors.lastname: Oh
authors.forename: Suk-Kyun
authors.initials: SK
authors.lastname: Yang
authors.forename: Sang Hyoung
authors.initials: SH
authors.lastname: Park
authors.forename: Jae Yong
authors.initials: JY
authors.lastname: Han
authors.forename: Sung Pil
authors.initials: SP
authors.lastname: Hong
authors.forename: Tae Il
authors.initials: TI
authors.lastname: Kim
authors.forename: Won Ho
authors.initials: WH
authors.lastname: Kim
authors.forename: Min Goo
authors.initials: MG
authors.lastname: Lee
mesh_terms: D000293:Adolescent; D000328:Adult; D016022:Case-Control Studies; D015331:Cohort Studies; D003424:Crohn Disease / Q000453:epidemiology* / Q000235:genetics*; D005260:Female; D005500:Follow-Up Studies; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D005838:Genotype; D015236:HLA-C Antigens / Q000235:genetics*; D006801:Humans; D008297:Male; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D015995:Prevalence; D056910:Republic of Korea / Q000453:epidemiology; D012307:Risk Factors; D053380:Tumor Necrosis Factor Ligand Superfamily Member 15 / Q000235:genetics*; D055815:Young Adult
chemical_list: D015236:HLA-C Antigens; C117026:TNFSF15 protein, human; D053380:Tumor Necrosis Factor Ligand Superfamily Member 15