Disease susceptibility genes shared by primary biliary cirrhosis and Crohn’s disease in the Japanese population View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2015-06-18

AUTHORS

Yoshihiro Aiba, Keiko Yamazaki, Nao Nishida, Minae Kawashima, Yuki Hitomi, Hitomi Nakamura, Atsumasa Komori, Yuta Fuyuno, Atsushi Takahashi, Takaaki Kawaguchi, Masakazu Takazoe, Yasuo Suzuki, Satoshi Motoya, Toshiyuki Matsui, Motohiro Esaki, Takayuki Matsumoto, Michiaki Kubo, Katsushi Tokunaga, Minoru Nakamura

ABSTRACT

We previously identified TNFSF15 as the most significant susceptibility gene at non-HLA loci for both primary biliary cirrhosis (PBC) and Crohn’s diseases (CD) in the Japanese population. The aim of this study is to identify further disease susceptibility genes shared by PBC and CD. We selected 15 and 33 genetic variants that were significantly associated with PBC and CD, respectively, based on previously reported genome-wide association studies of the Japanese population. Next, an association study was independently performed for these genetic variants in CD (1312 CD patients and 3331 healthy controls) and PBC (1279 PBC patients and 1015 healthy controls) cohorts. Two CD susceptibility genes, ICOSLG rs2838519 and IL12B rs6556412, were also nominally associated with susceptibility to PBC (P=3.85 × 10−2 and P=8.40 × 10−3, respectively). Three PBC susceptibility genes, CXCR5 rs6421571, STAT4 rs7574865 and NFKB1 rs230534, were nominally associated with susceptibility to CD (P=2.82 × 10−2, P=3.88 × 10−2 and P=2.04 × 10−2, respectively). The effect of ICOSLG and CXCR5 variants were concordant but the effect of STAT4, NFKB1 and IL12B variants were discordant for PBC and CD. TNFSF15 and ICOSLG-CXCR5 might constitute a shared pathogenic pathway in the development of PBC and CD in the Japanese population, whereas IL12B-STAT4-NFKB1 might constitute an opposite pathogenic pathway, reflecting the different balance between Th1 and Th17 in the two diseases. More... »

PAGES

525-531

Journal

TITLE

Journal of Human Genetics

ISSUE

9

VOLUME

60

Author Affiliations

  • Clinical Research Center, National Hospital Organization, Nagasaki Medical Center, Omura, Japan
  • Laboratory for Genotyping Development, Center for Integrative Medical Science, Institute of Physical and Chemical Research (RIKEN), Yokohama, Japan
  • The Research Center for Hepatitis and Immunology, National Center for Global Health and Medicine, Chiba, Japan
  • Japan Science and Technology Agency (JST), Tokyo, Japan
  • Department of Human Genetics, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
  • Department of Hepatology, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan
  • Department of Medicine and Clinical Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
  • Laboratory for Statistical Analysis, Center for Integrative Medical Sciences, RIKEN, Tokyo, Japan
  • Department of Medicine, Division of Gastroenterology, Tokyo Yamate Medical Center, Tokyo, Japan
  • Department of Internal Medicine, Faculty of Medicine, Toho University, Chiba, Japan
  • Department of Gastroenterology, Sapporo Kosei Hospital, Sapporo, Japan
  • Department of Gastroenterology, Fukuoka University Chikushi Hospital, Fukuoka, Japan
  • Division of Gastroenterology, Department of Internal Medicine, Iwate Medical University, Iwate, Japan
  • Headquarters of PBC Research in the National Hospital Organization Study Group for Liver Disease in Japan (NHOSLJ) and gp210 working in Research Program of Intractable Hepatoboliary Disease Study Group supported by the Ministry of Health, Labour, and Welfare of Japan, Clinical Research Center, National Hospital Organization Nagasaki Medical Center, Nagasaki, Japan
  • Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1038/jhg.2015.59

    DOI

    http://dx.doi.org/10.1038/jhg.2015.59

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1032394963

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/26084578


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