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HLA-C*01 is a Risk Factor for Crohn's Disease

 Jung, Eun Suk  ;  Cheon, Jae Hee  ;  Lee, Ji Hyun  ;  Park, Soo Jung  ;  Jang, Hui Won  ;  Chung, Sook Hee  ;  Park, Myoung Hee  ;  Kim, Tai-Gyu  ;  Oh, Heung-Bum  ;  Yang, Suk-Kyun  ;  Park, Sang Hyoung  ;  Han, Jae Yong  ;  Hong, Sung Pil  ;  Kim, Tae Il  ;  Kim, Won Ho  ;  Lee, Min Goo 
 INFLAMMATORY BOWEL DISEASES, Vol.22(4) : 796-806, 2016 
Journal Title
Issue Date
Adolescent ; Adult ; Case-Control Studies ; Cohort Studies ; Crohn Disease/epidemiology* ; Crohn Disease/genetics* ; Female ; Follow-Up Studies ; Genetic Predisposition to Disease ; Genome-Wide Association Study* ; Genotype ; HLA-C Antigens/genetics* ; Humans ; Male ; Polymorphism, Single Nucleotide/genetics* ; Prevalence ; Republic of Korea/epidemiology ; Risk Factors ; Tumor Necrosis Factor Ligand Superfamily Member 15/genetics* ; Young Adult
Crohn’s disease ; GWAS ; HLA ; inflammatory bowel disease
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.
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1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Pharmacology (약리학교실) > 1. Journal Papers
Yonsei Authors
Kim, Won Ho(김원호) ORCID logo https://orcid.org/0000-0002-5682-9972
Kim, Tae Il(김태일) ORCID logo https://orcid.org/0000-0003-4807-890X
Park, Soo Jung(박수정)
Lee, Min Goo(이민구) ORCID logo https://orcid.org/0000-0001-7436-012X
Jung, Eun Suk(정은석)
Cheon, Jae Hee(천재희) ORCID logo https://orcid.org/0000-0002-2282-8904
Hong, Sung Pil(홍성필)
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