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

Eun Suk Jung, JaeHee 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

Research output: Contribution to journalArticle

5 Citations (Scopus)

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

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HLA Antigens
Crohn Disease
KIR Receptors
Genome-Wide Association Study
Disease Susceptibility
Lymphotoxin-beta
Population
Mucosal Immunity
Intergenic DNA
Genetic Promoter Regions
Genes
Odds Ratio
Genotype

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Gastroenterology

Cite this

Jung, E. S., Cheon, J., Lee, J. H., Park, S. J., Jang, H. W., Chung, S. 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
Jung, Eun Suk ; Cheon, JaeHee ; 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. / HLA-C∗01 is a risk factor for Crohn's disease. In: Inflammatory Bowel Diseases. 2016 ; Vol. 22, No. 4. pp. 796-806.
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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.",
author = "Jung, {Eun Suk} and JaeHee Cheon and Lee, {Ji Hyun} and Park, {Soo Jung} and Jang, {Hui Won} and Chung, {Sook Hee} and Park, {Myoung Hee} and Kim, {Tai Gyu} and Oh, {Heung Bum} and Yang, {Suk Kyun} and Park, {Sang Hyoung} and Han, {Jae Yong} and Hong, {Sung Pil} and Kim, {Tae Il} and Kim, {Won Ho} and Lee, {Min Goo}",
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Jung, ES, Cheon, J, Lee, JH, Park, SJ, Jang, HW, Chung, SH, Park, MH, Kim, TG, Oh, HB, Yang, SK, Park, SH, Han, JY, Hong, SP, Kim, TI, Kim, WH & Lee, MG 2016, 'HLA-C∗01 is a risk factor for Crohn's disease', Inflammatory Bowel Diseases, vol. 22, no. 4, pp. 796-806. https://doi.org/10.1097/MIB.0000000000000693

HLA-C∗01 is a risk factor for Crohn's disease. / Jung, Eun Suk; Cheon, JaeHee; 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.

In: Inflammatory Bowel Diseases, Vol. 22, No. 4, 09.03.2016, p. 796-806.

Research output: Contribution to journalArticle

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T1 - HLA-C∗01 is a risk factor for Crohn's disease

AU - Jung, Eun Suk

AU - Cheon, JaeHee

AU - Lee, Ji Hyun

AU - Park, Soo Jung

AU - Jang, Hui Won

AU - Chung, Sook Hee

AU - Park, Myoung Hee

AU - Kim, Tai Gyu

AU - Oh, Heung Bum

AU - Yang, Suk Kyun

AU - Park, Sang Hyoung

AU - Han, Jae Yong

AU - Hong, Sung Pil

AU - Kim, Tae Il

AU - Kim, Won Ho

AU - Lee, Min Goo

PY - 2016/3/9

Y1 - 2016/3/9

N2 - 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.

AB - 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.

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