HLA-C∗01 is a risk factor for Crohn's disease

Eun Suk Jung, Jae Hee Cheon, Ji Hyun Lee, Soo Jung Park, Hui Won Jang, Sook Hee Chung, Myoung Hee Park, Tai Gyu Kim, Heung Bum Oh, Suk Kyun Yang, Sang Hyoung Park, Jae Yong Han, Sung Pil Hong, Tae Il Kim, Won Ho Kim, Min Goo Lee

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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 -23; 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.

Original languageEnglish
Pages (from-to)796-806
Number of pages11
JournalInflammatory Bowel Diseases
Volume22
Issue number4
DOIs
Publication statusPublished - 2016 Mar 9

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Gastroenterology

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    Jung, E. S., Cheon, J. H., Lee, J. H., Park, S. J., Jang, H. W., Chung, S. H., Park, M. H., Kim, T. G., Oh, H. B., Yang, S. K., Park, S. H., Han, J. Y., Hong, S. P., Kim, T. I., Kim, W. H., & Lee, M. G. (2016). HLA-C∗01 is a risk factor for Crohn's disease. Inflammatory Bowel Diseases, 22(4), 796-806. https://doi.org/10.1097/MIB.0000000000000693